We review aspects of the antibody response to SARS-CoV-2, the causative agent of the COVID- 19 pandemic. The topics we cover are relevant to immunotherapy with plasma from recovered patients and with monoclonal antibodies against the viral S-protein. The development of vaccines against SARS-CoV-2, an essential public health tool, will also be informed by an understanding of the antibody response in infected patients. Although virus-neutralizing antibodies are likely to protect, antibodies could potentially trigger immunopathogenic events in SARS-CoV-2-infected patients or enhance infection. An awareness of these possibilities may benefit clinicians and the developers of antibody-based therapies and vaccines.

The SARS-CoV-2 is a recently identified positive sense single stranded RNA virus and member of the coronavirus family of viruses. It is thought to be the etiological factor for the ongoing COVID-19 pandemic. This virus is thought to have originated from bats and acquired ability of human-to-human transmission. While SARS-CoV-2 is relatively benign, it has infected more than half a million people (as of March 29^th 2020) worldwide and the number of infected people continues to rise. More than 170 countries have reported COVID-19 positive cases. With a mortality rate of less than both the previous coronavirus outbreaks, COVID-19 has (conversely) caused the death of over 33,980 (as of 29^th March, 2020 at 22.00 hours EDT) people worldwide and the number is increasing. Given the enormous impact of this virus on human health and wellbeing and consequent devastating impacts on world trade, economics and quality of life, it is important to understand this virus better and get insight into its pathogenic mechanisms which will aid in devising effective measure to curb its spread and predict future pattern of its interaction with humans. Though very little is known about this SARS-CoV-2 but its mechanisms and patterns of spread can be speculated (with caution, nevertheless) from what we know about its closest relatives SARS-CoV-1 (responsible for SARS-2002 epidemic) and MERS-CoV (responsible for MERS-2012 epidemic). In the present review, we aim at bringing together the coherent and peer reviewed literature about the SARS-CoV-2 and its close relatives and try to understand its infection patterns and reconstruct its pathogenic mechanisms with anecdotes on diagnosis and future directions. We hope that this paper will serve the purpose of being a reliable source of information to scientists, clinicians and general public.

In this report, we demonstrate that it is possible to design epitope-based peptide vaccine candidates to counteract the novel China coronavirus (2019-nCoV) by using an approach similar to the one used in cancer neoantigen vaccination therapy. We identified multiepitope peptide vaccine candidates against 2019-nCov that can potentially trigger both CD4⁺ and CD8⁺ T cell immune response with increased efficiency due to the presence of CD4⁺ and CD8⁺ T cell epitopes and a cathepsin-sensitive linker. Furthermore, we suggest that the peptide design strategy should incorporate population-specific HLA alleles in order to optimize binding specificity of the peptides. We refer to this as populationalized vaccinomics.

We aimed to evaluate the safety of maternal Tdap we assessed health events by examining the difference in birth and hospital-related outcomes of infants with and without fetal exposure to Tdap. This was a retrospective cohort study using linked administrative datasets. The study population were all live-born infants in New Zealand (NZ) weighing at least 400 grams at delivery and born to women who were eligible for the government funded, national-level vaccination program in 2013. Infants were followed from birth up to one year of age. There were a total of 69,389 eligible infants in the cohort. Of these, 8,299 infants were born to 8,178 mothers exposed to Tdap (12%), primarily between 28-38 weeks gestation as per the national schedule. Among the outcomes, we found a reduced risk for moderate to late preterm birth, low birth weight, small for gestational age, large for gestational age, respiratory distress syndrome, transient tachypnea of newborn, tachycardia or bradycardia, haemolytic diseases, other neonatal jaundice, anaemia, syndrome of infant of mother with gestational diabetes, and hypoglycemia in infants born to vaccinated mothers. There was no association between maternal Tdap and stillbirth, infant Apgar score at 5 minutes after birth, microcephaly, asphyxia, sepsis or infection, or hypoxic ischemic encephalopathy. Infant exposure to Tdap during pregnancy was associated with a higher mean birthweight (not clinically significant) and higher odds for ankyloglossia and neonatal erythema toxicum diagnoses. There were insufficient observations to allow examination of the effect of Tdap on extreme preterm and very preterm birth, and infant death. Overall, we found no outcomes of concern associated with the administration of Tdap during pregnancy.

High throughput multiplex serological systems enable the small developer to set up tests at small cost, for microbes for which there are no commercial tests, and for aspects which have not been addressed by them. An example is testing for Zika and Tick Borne Encephalitis virus antibodies, where antigenic cross-reactions make diagnosis problematic. Our technique variant, Suspension Multiplex Immunoassay (SMIA) allows many samples to be tested for antibodies to many antigens in a short time. Computational compensation for cross-reactions is possible if a SMIA panel contains most of the potentially cross-reacting antigens. Using antibody avidity and pattern of reactivity to whole virus and nonstructural protein, antibodies due to vaccination and infection, respectively, as well as probable degree of protection, can be determined with high throughput. These multiplex techniques hold great promise for future diagnostic development. Theoretically, even large scale serological monitoring, like blood donor pathogen testing, could be done inexpensively and rationally with multiplex serology developed in house. However, the quality control demands are steep and in most cases out of scope for a single laboratory. There remain however a number of clinical applications where in house multiplex serology can be performed with adequate quality control under high throughput conditions.

Sporotrichosis is a subcutaneous mycosis affecting humans and other animals that can be transmitted a zoonosis with cats as the main vector. The conventional anti-fungal therapy is especially inefficient in immunocompromised patients, who tend to develop the most severe forms of the disease, thus prompting the search for alternative therapies. Given their antigen-presenting properties, dendritic cells (DCs) have been used in both prophylactic and therapeutic vaccination strategies. Hence, this study aims to assess the use of DCs as a prophylactic tool in sporotrichosis by evaluating the immune profile induced by Sporothrix schenckii cell wall proteins (SsCWP)-stimulated bone-marrow-derived DCs (BMDCs). Mouse BMDCs were stimulated with SsCWP for 24 hours and analyzed for the surface expression of co-stimulatory molecules and TLR-4, as well as the secretion of proinflammatory cytokines and IL-10. Following that, activated BMDCs were cocultured with splenocytes for 72 hours and had the same cytokines measured in the supernatant. SsCWP-stimulated BMDCs showed higher expression of CD80, CD86, and CD40, but not TLR-4, and higher secretion of IL-6, IL-17A, and TNF. On the other hand, higher levels of IFN-γ, IL-10, and IL-2 were found in the supernatants of the coculture as compared with the BMDCs alone; TNF secretion was almost completely abrogated, whereas IL-6 was only partially inhibited and IL-17A was unaffected. Our results thus suggest SsCWP-stimulated BMDCs are able to induce a Th1-prone cytokine profile, known to be protective against other fungal diseases. This result could lead to evaluate the development of prophylactic and/or therapeutic DC-based tools against sporotrichosis.

Avian infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis, which causes considerable economic losses to the poultry industry worldwide. It is imperative to develop safe and efficient candidate vaccines to control IBV infection. In the current study, recombinant baculoviruses co-expressing S1 and N proteins, mono-expressing S1 or N proteins alone of IBV were constructed and prepared into subunit vaccines rHBM-S1-N, rHBM-S1 and rHBM-N. The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, boosting with the same dose 14 days later, and following challenge with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). The commercial vaccine strain H120 was used as a control. The IBV-specific antibody levels as well as the percentages of CD4+ and CD8+ T lymphocytes were detected within 28 days post-vaccination (dpv). The morbidity, mortality, and re-isolation of virus from the tracheas and kidneys of challenged birds were evaluated at 5 days post-challenge (dpc). The results showed that the IBV-specific antibody levels and the percentages of CD4+ and CD8+ T lymphocyte in rHBM-S1-N group were higher than those of rHBM-S1 and rHBM-N groups, especially the cellular immunity response. At 5 dpc, the mortality, morbidity and virus re-isolation rate of rHBM-S1-N were slightly higher than those of H120 group, but were lower than those of rHBM-S1 group and rHBM-N group. The present study demonstrated that the protection of recombinant baculovirus co-expressing S1 and N proteins was better than that of recombinant baculoviruses mono-expressing S1 or N protein alone. Thus, the recombinant baculovirus co-expressing S1 and N proteins could serve as a potential IBV vaccine and this demonstrates that the bivalent subunit vaccine including the S1 and N proteins might be a strategy for the development of an IBV subunit vaccine.

Neisseria meningitidis causes most cases of bacterial meningitis. Meningococcal meningitis is a public health burden to both developed and developing countries throughout the world. There are a number of vaccines (polysaccharide-based, glycoconjugate, protein-based and combined conjugate vaccines) that are approved to target five of the six disease-causing serogroups of the pathogen. Immunization strategies have been effective at helping to decrease the global incidence of meningococcal meningitis. Researchers continue to enhance these efforts through discovery of new antigen targets that may lead to a broadly protective vaccine and development of new methods of homogenous vaccine production. This review describes current meningococcal vaccines and discusses some recent research discoveries that may transform vaccine development against N. meningitidis in the future.

Micro lens arrays (MLAs) play a critical role in optical imaging, new energy technologies, and advanced displays. In this work, high-quality micro lens arrays with controllable profiles using femtosecond-laser-induced modification assisted wet etching (FLIM-WE) were fabricated. The effects of laser single-pulse energy, pulse number, and hydrofluoric acid etching duration on micro lens profiles were systematically studied. Optimization of these parameters enabled the successful preparation of dimensionally controlled micro lens arrays with stable performance and excellent surface quality on fused silica substrates. Ultimately, two types of micro lens arrays were fabricated using femtosecond laser-assisted wet etching. These arrays demonstrated exceptional uniformity and surface quality (Ra~100nm), facilitating clear imaging at various magnifications, with an adjustment range of 1.3X~3.0X. This provides a potential technical support for special micro-optical systems.

In the realm of high-pressure vessel simulation, conventional finite element method (FEM) approaches, as per ASME standards, may inadequately predict the behavior of flat surfaces under elevated temperatures. This study challenges the efficacy of shell-type mesh modeling for high-temperature flat plates, demonstrating that the thermal conditions within such high-pressure vessels can induce thermal instability and buckling, not accounted for by traditional FEM methods recommended by ASME. Through comprehensive analytical investigations, we reveal that traditional shell-type meshing techniques, while suitable for certain applications, fail to capture the intricate thermal stresses and deformation patterns inherent in high-temperature flat plate configurations. Our analysis delineates distinct stability regimes governed by key design parameters—including plate thickness, operating temperature, and geometric dimensions—profoundly impacting the structural integrity of heating plates under thermal loading. By elucidating these stability boundaries, this research provides engineers with critical insights necessary for optimizing the design and performance of high-temperature equipment. This includes the design of high-pressure vessels with flat surfaces for heating materials, flanges in high-temperature environments, and fins in heat exchangers across various industries such as oil and gas, pyrolysis, and power plants. The findings presented herein serve as a valuable reference for engineers seeking to comprehend and mitigate instability phenomena in solid mechanics, offering practical guidance for developing robust and reliable high-temperature structures in demanding industrial environments.

Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as donor shortage in heart transplantation, and infection, stroke, or gastrointestinal bleeding in LVADs. Therefore, alternative therapeutic strategies are still needed. In this respect, stem cell therapy has been introduced for the treatment of HF and numerous preclinical and clinical studies using various types of stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to improve cardiac function and attenuate left ventricular remodeling. IPSCs, which have a capacity of unlimited proliferation and differentiation to cardiomyocytes, are a promising cell source for myocardial regeneration therapy. This review discusses the current status of cardiac regenerative therapy using iPSCs.

Pluripotent stem cells (PSCs) can differentiate into three germ layers and diverse autolo-gous cell lines. Being among the most commonly used large domesticated hoofed animals and serving as a vital source of food and bioreactors, cattle are among the many species in which PSCs have been developed. Bovine PSCs (bPSCs) are the "seed cells" of regenerative science and have immense potential to advance species propagation, genetic engineering, and disease treatment. Moreover, they can aid in screening new drugs for efficacy and toxicity, model human diseases, and establish a sustainable agricultural system that can cater to the needs of the growing global population. Establishing stable bPSCs in vitro has been a critical scientific challenge, and researchers have made numerous attempts to address this issue. This review primarily delves into the current research progress of bPSCs, the challenges faced, and their potential applications.

During geomagnetic storms, which are a result of solar wind interaction with the Earth’s magnetosphere, geomagnetically induced currents (GICs) begin to flow in the long-distance high-voltage power grids on the Earth’s surface. It causes a number of negative phenomena that affect the normal operation of the entire electric power system. To investigate the nature of the phenomenon and its possible effects on transformers, a GIC monitoring system was created in 2011, the devices of which were installed at five substations of the Kola-Karelian power transit in northwestern Russia. Over 12 years of operating the system a large amount of data has been accumulated, which cannot be analyzed manually within a reasonable amount of time. To analyze the constantly growing volume of recorded data effectively, a method for automatic classification of GIC in autotransformer neutral was proposed. The method is based on a continuous wavelet transform of the neutral current data combined with a convolutional neural network (CNN) to classify the obtained scalogram images. As the result of comparing four CNNs with different architectures, a model that showed excellent GIC classification performance on the validation set (100.00% accuracy and loss of 0.0115) was chosen.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a complex gastrointestinal disorder with a multifactorial etiology, including environmental triggers, autoimmune mechanisms, and genetic predisposition. Despite advancements in therapeutic strategies for IBD, its associated mortality rate continues to rise, which is often attributed to unforeseen side effects of conventional treatments. In this context, we explored the potential of Ecklonia cava extract (ECE) derived from an edible marine alga known for its anti-inflammatory and antioxidant properties in mitigating IBD. This study investigated the effectiveness of ECE as a preventive agent in a murine model of dextran sulfate sodium (DSS)-induced colitis. Our findings revealed that pretreatment with ECE significantly ameliorated colitis severity as evidenced by increased colon length, reduced spleen weight, and histological improvements demonstrated by immunohistochemical analysis. Furthermore, ECE significantly attenuated the upregulation of inflammatory cytokines and mediators and the infiltration of immune cells known to be prominent features of colitis in mice. Notably, ECE restored dysbiosis of intestinal microflora and aided in the recovery of damaged intestinal mucosa. Mechanistically, ECE exhibited protective effects against pathogenic colitis by inhibiting the NLRP3/NF-κB pathway known to be pivotal regulators in the inflammatory signaling cascade. These compelling results suggest that ECE holds promise as a potential candidate for IBD prevention. It might be developed into a functional food for promoting gastrointestinal health. This research sheds light on the preventive potential of natural compounds like ECE in the management of IBD, offering a safer and more effective approach to combating this challenging disease.

Vibrations of plate structures placed in a supersonic flow is considered. The undisturbed fluid flow is parallel to the plate. Two specific problems are treated: in the first one the plate is in the form of an infinite strip and the flow is in the direction of its finite length. Rigid walls extend from the sides of the plate indefinitely. In the second problem, the plate is a finite rectangle and the flow is parallel to one of its sides. The first problem is a limiting case of the second problem. The flow is modeled by piston theory which assumes that the fluid pressure on the plate is proportional to local slope. This approximation is widely used at high speeds, and reduces the interaction between the fluid flow and the vibrations of the plate to an additional term in the vibration equation. The resulting problem can be solved by assumed mode methods. In this study, the solution is also carried out by using the collocation method. The main result is the flutter velocity of the free fluid flow under which the plate vibrations become unstable. Finally, simple expressions are proposed between the various non-dimensional parameters that allows quick estimation of flutter velocity.

The present paper describes a study case of the failure investigation of Duplex stainless steel (UNS S31803) on the tube and tube sheet section of a shell and tube heat exchanger BEM TEMA type with seawater as the cooling medium. Although UNS S31803 offers high strength, high resistance to chloride-induced SCC, and high resistance to pitting attack in chloride environments, in this study case, the heat exchanger experienced some material degradation; 26 tubes were leaked and plugged on both sides, and scales plugged 76 tubes. The examination in this study case revealed the formation of biofilm inside the tubes, XRD examination revealed that the film contained aragonite (CaCO3), and by using microstructural examination on the inner surface of the tube, the austenite grains were preferentially attacked by crevice corrosion. In this case, the failure was caused by crevice corrosion, and crevice corrosion was enhanced by microbiological-induced corrosion (MIC). Recommendations to avoid similar failures are also suggested in this paper.

In recent years, laser engraving has received widespread attention as a convenient, efficient, and programmable method, which has enabled the obtaining of high-quality porous graphene from various precursors. Laser engraving is often used to fabricate the dielectric layer with micro-structure for capacitive pressure sensors, however, the usual choice of electrodes remains poorly flexible metal electrodes, which greatly limits the overall flexibility of the sensors. In this work, we propose a flexible capacitive pressure sensor made entirely of thermoplastic polyurethane (TPU) and laser-induced graphene (LIG) derived from wood. The capacitive pressure sensor consisted of a flexible LIG/TPU electrode (LTE), a LIG/TPU electrode with micro hole array, and dielectric layer of TPU with micro-cone array molded from laser-engraved hole array on wood, which provided high sensitivity (0.11 kPa-1), ultra-wide pressure detection range (100Pa to 1.4MPa), fast response (~300 ms) and good stability (>4000 cycles, at 0-35 kPa). We believe that our research makes a significant contribution to the literature because the easily available materials derived from wood and overall consistent flexibility meet the requirements of flexible electronic devices.

A 3D graphene foam made of interconnected multilayer graphene flakes was produced on optical fibres (OF) by laser-induced transformation of a polyimide (PI) film coated on the OF cladding. This material, known as la-ser-induced graphene (LIG), was explored in the electrochemical detection and quantification of dopamine (DA) at physiologically relevant concentrations in the presence of the most relevant interfering molecules in biological fluids, ascorbic acid (AA) and uric acid (UA). The measured limit of detection is 100 nM, the linear range is 0.1 to 5 μM and a maximum sensitivity of 5.0 µA µM−1 cm−2 was obtained for LIG decorated with Pt nanoparticles (NPs). Moreover, immunity to AA and UA interference and to fouling was attained by decorating the LIG elec-trode with Pt NPs and coating with Nafion. These figures of merit underlines the potential of these sensors for the quantification of physiologically relevant concentrations of DA in biological fluids, paving the way for the development of hybrid electrochemical/optical sensing actuating platforms in a lab-on-fibre configuration, with relevant applications in biomedical engineering. The advantages of this hybrid arrangement include the possi-bility of in-situ counterproofing, extended measuring ranges, photoelectrochemical detection and the probing of inaccessible places. This elegant approach can also provide a simple and cost-effective way to fabricate biomed-ical devices with extended functionality, such as medical optical probes with added electrochemical capabilities, optogenetics combined with local electrochemical detection, among others.

The fall armyworm (FAW), Spodoptera frugiperda, has become one of the most important pests on corn in China since it invaded in 2019. Although FAW has not been reported to cause widespread damage to rice plants in China, it has been sporadically found feeding in the field. If FAW infests rice in China, the fitness of other insect pests on rice may be influenced. However, how FAW and other insect pests on rice interact remains unknown. In this study, we found that the infestation of FAW larvae on rice plants prolonged the developmental duration of the brown planthopper (BPH, Nilaparvata lugens (Stål)) eggs, and plants damaged by gravid BPH females did not induce defenses that influenced the growth of FAW larvae. Moreover, co-infestation by FAW larvae on rice plants did not influence the attractiveness of volatiles emitted from BPH-infested plants to Anagrus nilaparvatae, an egg parasitoid of rice planthoppers. FAW larvae were able to prey on BPH eggs laid on rice plants and grew faster compared to those larvae that lacked available eggs. Studies revealed that the delay in development of BPH eggs on FAW-infested plants was probably related to the increase in levels of jasmonoyl-isoleucine, abscisic acid and the defensive compounds in the rice leaf sheaths on which BPH eggs were laid. These findings indicate that if FAW invades rice plants in China, the population density of BPH may be decreased by intraguild predation and induced plant defenses, whereas the population density of FAW may be increased.

The current study aimed to investigate the antitumor effects and potent mechanism of cytokine-induced killer (CIK) cells combined with irreversible electroporation (IRE) via an in vitro function assay in an in vivo Panc02 cell–bearing mouse model. We established an in vitro culture assay for CIK cells and determined the proportions of different peripheral lymphocytes. The antitumor effect of the combination of IRE and CIK cells in a Panc02 pancreatic-cancer (PC) subcutaneous-xenograft model was investigated; tumor size and mouse survival rates were recorded. We used flow cytometry (FCM) to analyze the proportion of intratumoral lymphocytes, the expression of chemokine receptors, and the proliferative activity of CIK cells. The proportion of cells that were positive for clusters of differentiation 3 and 8 (CD3+CD8+) and the proportion of CD3+CD56+ cells were both significantly increased after 21 days of in vitro culture. Combined IRE/CIK cell treatment significantly inhibited tumor growth and increased the survival rate of Panc02 cell–bearing mice. Furthermore, infiltration of lymphocytes into tumor tissue was significantly increased by this combination therapy compared with the untreated group or monotherapy group. In addition, IRE significantly enhanced the expression of chemokine receptors elicited by, and the proliferative activity of, CIK cells. In conclusion, IRE combined with CIK cells showed superior antitumor efficacy in a PC subcutaneous-xenograft model, which we attributed to the promotion of lymphocytic infiltration, as well as to upregulation of chemokine receptor expression and of regulators of CIK cell proliferation.

Background: Despite the existence of a wide variety of anti-inflammatory drugs, the vast majority are classified as steroidal or non-steroidal. Both classes with many side effects that limit usage. Thus, the search for new molecules with anti-inflammatory potential is still important. Methods: Five phenylbenzohydrazides were synthetized and evaluated in pre-clinical models of acute inflammation in vivo and in vitro. Results: Substances significantly reduced cell migration induced by carrageenan. It was also observed an intense inhibition in protein extravasation and cytokines (IL-6, IL-1β, and TNF-α) production as well as nitric oxide reduction. INL-11 demonstrated to be the most potent since the reduction was significant even when compared with dexamethasone. In vitro INLs also reduced cytokines and NO production and iNOS activity. INL-11 was the most effective in reducing cell migration in vitro. Conclusions: our data suggest that these substances are suitable for further development to new series of compounds that could lead to new hits and future drug prototypes for anti-inflammatory conditions.

Although lithium-ion batteries have extensively been used in various applications because of their high energy capacity, fracture and failure, the by-products of large strains and stresses caused by fast charging and discharging need yet to be addressed. The size effects on the mechanical behavior of the nano-sized structures are significant; however, the classical elasticity theory may not consider such effects. On the other hand, surface stress theory, as a robust and potential theory, is suitable in considering size effects in nano-scale structures. Therefore, in this paper, in order to involve the surface stress effects on the fracture behavior of Li-ion batteries, the following steps are taken. Firstly, a phase-field model is used to determine the evolution of the concentration profile. Subsequently, the stress distribution is obtained by using the surface stress theory combined with chemical equations for a planar electrode. Afterward, by using the weight function method for an edge crack in the plate, the stress intensity factor is derived for all time steps and possible crack lengths during the process. It is found that with increasing phase boundary thickness parameter or decreasing phase-separation phenomenon, the surface mechanics parameters become more influential. Furthermore, in the presence of positive surface stress, the diffusion-induced stress distribution decreases, which in turn reduces the stress intensity factor. In addition, in this paper, the two states of surface stress are compared either for elastic or total strain. Concerning stresses and concentrations, the results indicate a big difference at the beginning of the deintercalation process showing, in particular, 2% for stresses, but the differences diminish gradually.

Arboviruses of medical and veterinary significance have been identified on all 7 continents with every human and animal population at risk for exposure. Like arboviruses, chronic neurodegenerative diseases like Alzheimer’s and Parkinson’s disease are found wherever there are humans. Viral parkinsonism has been documented for a variety of human pathogens though there are few studies that evaluate the effects of viral infection on degenerative neurological diseases. Significant differences in baseline gene and protein expression have been determined between Human Induced Pluripotent Stem Cell lines derived from a non-Parkinson’s disease individual and from an individual with reported Parkinson’s disease. While the organoids generated from each cell line were physically indistinguishable, significant differences were observed in gene and protein expression for neurotransmission and immunity. It was hypothesized that these inherent differences would impact cerebral organoid responses to viral infection. In this preliminary observational study, cerebral organoids from a non-Parkinson’s and Parkinson’s patient were infected with Chikungunya virus and observed for 2 weeks. Parkinson’s organoids lost mass and exhibited a dysfunctional antiviral response. Neurotransmission data from both non-Parkinson’s and Parkinson’s organoids had dysregulation of IL-1, IL-10, IL-6. These cytokines are associated with mood and could be contributing to persistent depression seen in patients following CHIKV infection. Both organoid types had increased expression of CCR5 and CXCL10 which are linked to demyelination, highlighting a potential mechanism for virus-associated parkinsonism. The dysfunctional antiviral response of Parkinson’s organoids highlights the need for more research in neurotropic infections in a neurologically compromised host.

The development of 3D cerebral brain organoids which accurately resemble aspects of the human brain permits a more accurate characterization of physiological processes and neurological diseases. Cerebral organoids can be grown from stem cell lines with various genetic backgrounds allowing multiple neurodegenerative diseases to be modeled. While dysfunction in neurotransmission of patients with neurodegenerative diseases is expected, the impact of chronic neurodegeneration on the response to viral infection of the CNS is poorly understood. For instance, several mosquito-borne viruses like Dengue virus and West Nile Virus cause post-viral parkinsonism. How CNS infection might impact a host with inherent CNS dysfunction such as Parkinson’s Disease in poorly understood. This preliminary, observational study aimed to understand dysfunction in intrinsic and innate expression of a patient with a neurodegenerative disease and a non-affected individual in relation to potential viral infection in the CNS. Cerebral organoids were generated from human induced pluripotent stem cells with a normal genetic background or with idiopathic Parkinson’s Disease. After differentiation and maturation, organoid size, gene expression and immunofluorescence were evaluated to assess neurotransmission and innate immunity. While there was no significant difference in size of the organoids with a normal or Parkinson’s genetic background, gene expression studies identified multiple differences in innate immunity and neurotransmission. Immunofluorescence also identified differences in protein expression related to neurotransmission and innate immunity. Of note, organoids derived from a Parkinson’s patient exhibited endogenous up-regulation of dopamine and muscarinic acetylcholine receptors, GABA, glycine, and glutamate targets, and the majority of cytokines. This expression pattern suggests a chronic state of neuroexcitation and neuroinflammation in this population of organoids.

Introduction: Valproic acid (VPA) is an antiepileptic drug extensively used for treating partial and generalised seizures, acute mania and as prophylaxis for bipolar disorder. Drug-induced liver injury (DILI) persists as a significant issue related to fatal outcomes by VPA. The aim of this study was to increase our knowledge about this condition and to better identify patients affected. Methods: We conducted an observational retrospective case-control study that identified cases of DILI by VPA from the Pharmacovigilance Programme from our Laboratory Signals at La Paz University Hospital from January 2007 to December 2019. From the Therapeutic VPA Monitoring Programme, two control groups were assigned, VPA-tolerant patients and the other with patients who developed mild VPA-related hepatitis but who did not meet the DILI criteria, matched for date, age and sex. Results: A total of 60 patients were included in the study: 15 cases of DILI, 30 VPA-tolerant controls and 15 controls with mild hepatitis. Mean age for the cases was 45.7 years, 4(26.7%) were women and 5(33.34%) were children under 18 years, of them 3(20%) were fatal. Polytherapy with other antiepileptic drugs (p=0.047) and alcohol consumption (p<0.001) were associated with a greater risk of developing DILI by VPA. A diagnosis of epileptic seizure was more frequently related to DILI when compared with the VPA-tolerant controls (p<0.001). The cases developed hepatocellular hepatitis (p<0.001), while the mild hepatitis controls had a higher rate of cholestatic hepatitis (p<0.001). The laboratory lactate dehydrogenase values were statistically higher (even at baseline) in patients with DILI than in both control groups (p= 0.033 and p=0.039). Conclusions: VPA hepatotoxicity remains a considerable problem. This study offers interesting findings for characterising VPA-induced liver injury and at-risk patients.

It is important to distinguish between natural earthquakes and those induced by CO2 injection at carbon capture and storage sites. For example, the 2004 Mw 6.8 Chuetsu earthquake occurred close to the Nagaoka CO2 storage site during gas injection, but we could not quantify whether the earthquake was due to CO2 injection or not. Here we simulated changes of pore pressure during CO2 injection at the Nagaoka site and compared them with estimated natural seasonal fluctuations of pore pressure due to rainfall and snowmelt as well as estimated pore pressure increases related to remote earthquakes. We clearly distinguished changes of pore pressure due to CO2 injection from those due to rainfall and snowmelt. The simulated local increase in pore pressure at seismogenic fault area was much less than the seasonal fluctuations related to precipitation and increases caused by remote earthquakes, and the lateral extent of pore pressure increase was insufficient to influence seismogenic faults. We also demonstrated that pore pressure changes due to distant earthquakes are capable of triggering slip on seismogenic faults. The approach we developed could be used to distinguish natural from injection-induced earthquakes and will be useful for that purpose at other CO2 sequestration sites.

We report on space-selective crystallization of congruent and polar Sr2TiSi2O8 crystals in a stoichiometric SrO-TiO2-SiO2 glass induced by (1030 nm, 300 fs) femtosecond laser irradiation. This allows us to compare with non-congruent laser induced crystallization of polar LiNbO3, in non stoichiometric Li2O-Nb2O5-SiO2 glass and gain information on the mechanism of nanocrystals orientation with the laser polarization that we pointed out previously. Using scanning electron microscopy (SEM), Second-harmonic generation (SHG) and electron backscattered diffraction (EBSD), we studied the laser induced crystallization according to the laser processing parameters (pulse energy, pulse repetition rate, scanning speed). We found 1) a domain where the laser track is filled with crystals not perfectly textured (low energy), 2) a domain where an amorphous volume remain surrounded by a crystallized shell (high energy). This arises from Sr out-diffusion and may gives rise to crystallization of both SrTiO3 and Sr2TiSi2O8 phases at low speed. In the one-phase domain (at higher speed), it is found the possibility to elaborate a tube with a perfect fresnoite texture. Significant difference in size and morphology whereas crystallization threshold remains similar are discussed based on glases thermal propeties. Contrarily to Li2O-Nb2O5-SiO2 (LNS) glass, no domain of oriented nanocrystallization controlled by the laser polarization has been found in SrO-TiO2-SiO2 (STS) glass, which is attributed to the larger crystallization speed in STS glass. No nanogratings have also been found that is likely due to the congruency of the glass.

Inertial focusing conditions of fluorescent polystyrene spherical particles are studied at the pointwise level along their pathlines. This is accomplished by an algorithm that calculates a de-gree of spreading function of the particles' trajectories taking streaklines images as raw data. Different confinement ratios of the particles and flow rates are studied and the results are pre-sented in state diagrams showing the focusing degree of the particles in terms of their position within a curve of an asymmetric serpentine and the applied flow rate. In addition, together with numerical simulation results, we present empirical evidence that the preferred trajectories of inertially focused spheres are contained within Dean vortices' centerlines. We speculate about the existence of a new force, never postulated before, to explain this fact.

Polyvinyl alcohol-engineering cementitious composites (PVA-ECC) has been widely applied in bridge deck repairing or widening, the common practice for doing this is that a portion of a bridge is left open to traffic while the closed portion is constructed, which expose the early age PVA-ECC to the vehicle-induced vibrations. However, whether vehicle-induced vibrations affect the tensile performance of early age PVA-ECC remains unknow. The purpose of this study was to conduct laboratory test programs on how much vehicle-induced vibrations during early ages affected the tensile performance of PVA-ECC. A self-improved device was used to simulate the vehicle-induced vibrations, and after vibrating with the designed variables, both a uniaxial tensile test and a grey correlation analysis were performed. The results indicated that: the effects of vehicle-induced vibrations on the tensile performance of early age PVA-ECC were significant, and they generally tended to be negative in this investigation. In particular, for all of the vibrated PVA-ECC specimens, the most negative age when vibrated occurred during the period between the initial set and the final set. We concluded that although vehicle-induced vibrations during the setting periods had no substantial effects on the inherent strain-hardening characteristics of PVA-ECC, the effects should not be ignored.

In this paper, we synthesized MC(BeA-co-MMA) copolymer microcapsules through suspension polymerization. The pendent n-behenyl group of BeA is highly crystalline, and it acts as the side-chain in the structure of BeA-co-MMA copolymer. The highly crystalline n-behenyl side-chain provides BeA-co-MMA copolymer thermal-energy-storage capacity. In order to investigate the correlation between thermal properties and crystal structure of BeA-co-MMA copolymer, the effects of monomer ratio, temperature changing and changing rate, as well as synthesis method were discussed. The monomer ratio influenced crystal transition behavior and thermal properties greatly. The DSC results proved that when the monomer ratio of BeA and MMA was 3:1, MC(BeA-co-MMA)3 showed the highest average phase change enthalpy ΔH (105.1 J·g–1). It indicated that the n-behenyl side-chain formed relatively perfect crystal region, which ensured a high energy storage capacity of copolymer. All the DSC and SAXS results proved that the amount of BeA had a strong effect on the thermal-energy-storage capacity of copolymer and the long spacing of crystals, but barely on the crystal lamella. It was found that MMA units worked like defects in the n-behenyl side-chain crystal structure of BeA-co-MMA copolymer. Therefore, a lower fraction of MMA, that is, a higher fraction of BeA contributed to a higher crystallinity of BeA-co-MMA copolymer for providing a better energy storage capacity and thermoregulation property. ST(BeA-co-MMA) copolymer sheets with the same ingredients as microcapsules were also prepared through light-induced polymerization aiming at clarifying the effect of synthesis method. The results proved that synthesis method mainly influenced the copolymer chemical component, but lightly on the crystal packing of n-behenyl side-chain.

Q-switched laser radiation at wavelengths of 355 nm, 532 nm, and 1064 nm from a Nd: YAG laser was used to generate plasma in laboratory air at the target surface made of compressed nano-silver particles of size 95 ± 10 nm. The emitted resonance spectra from the neutral silver at wavelengths of 327.9 nm and 338.2 nm indicate existence of self-reversal in addition to plasma self-absorption. Both lines were identified in emission spectra at different laser irradiation wavelengths with characteristic dips at the un-shifted central wavelengths. These dips are usually associated with self-reversal. Under similar conditions, plasmas at the corresponding bulk silver target were generated. The recorded emission spectra were compared to those obtained from the nano-material target. The comparisons confirm existence of self-reversal of resonance lines that emerge from plasmas produced at nano-material targets. This work suggests a method for recovery of the spectral line shapes and discusses practical examples. In addition, subsidiary calibration efforts that utilize the Balmer series Hα-line reveal that other Ag I lines at 827.35 nm and 768.7 nm are optically thin under variety of experimental conditions and are well-suited as reference lines for measurement of the laser plasma electron density.

In this research, the computational fluid dynamic (CFD) approach that has been used in wind power generation field was applied for the solution of the problems of local strong wind areas in railway fields, and the mechanism of wind generation was discussed. At the same time, the affectivity of the application of computational fluid dynamic approach to railway field was discussed. The problem of local wind that occurs on the railway line in winter was taken up in this research. A computational simulation for the prediction of wind conditions by LES was implemented and it was clarified that the local strong wind area is mainly caused by separated flows originating from the small‐scale terrain positioned at its upstream (at approximately 180.0 m above sea level). Meanwhile, the effects of the size of calculation area and spatial grid resolution on the result of calculation and the effect of atmospheric stability were also discussed. It was clarified that when the air flow characteristic of the separated flow originating from the small‐scale terrain (at altitude of approximately 180.0 m) targeted in this research is reproduced at high accuracy by computational simulation of wind conditions, approximately 10.0 m of spatial resolution of computational grid in horizontal direction is required. As a result of the computational simulation of wind conditions of stably stratified flow (Fr = 1.0), lee waves were excited at the downstream of the terrain over time. As a result, the reverse‐flow region lying behind the terrain that had been observed at a neutral time was inhibited. Consequently, local strong wind area was generated at the downstream of the terrain and the strong wind area passing through the observation mast was observed. By investigating the speed increasing rate of local strong wind area induced at the time of stable stratification, it was found that the wind was approximately 1.2 times stronger than what was generated at a neutral time.

Electrically conductive polymer composites are in high demand for modern technologies, however, the intrinsic brittleness of conducting conjugated polymers and the moderate electrical conductivity of engineering polymer/carbon composites have highly constrained their applications. In this work, super high electrical conductive polymer composites were produced by a novel hot embossing design. The polydimethylsiloxane (PDMS) composites containing short carbon fiber (SCF) exhibited an electrical percolation threshold at 0.45 wt%, and reached a saturated electrical conductivity of 49 S/m at 8 wt% of SCF. When reduced the sample thickness from 1.0 mm to 0.1 mm by the hot embossing process, a compression-induced percolation threshold occurred at 0.3 wt%, while the electrical conductivity was further enhanced to 378 S/m at 8 wt% SCF. Furthermore, the additional of a second nanofiller of 1 wt%, such as carbon nanotube or conducting carbon black further increased the electrical conductivity of the PDMS/SCF (8 wt%) composites to 909 S/m and 657 S/m, respectively. The synergy of the densified conducting filler network by the mechanical compression and the hierarchical micro-/nanoscale filler approach has realize super high electrical conductive yet mechanical flexible polymer composites for modern flexible electronics applications.

This work communicates results from optical emission spectroscopy following laser-induced optical breakdown at or near nanomaterial. Selected atomic lines of silver are evaluated for consistent determination of electron density. Comparisons are presented with Balmer series hydrogen results. Of particular interest are measurements free of self-absorption effects. For several silver lines, asymmetries are observed in the recorded line profiles. Electron densities of interest range from 0.5 to 3 × 10¹⁷ cm^-3, for 5 nanosecond Q-switched Nd:YAG radiation at wavelengths of 1064, 532, and 355 nm, and for selected silver emission lines including 328.0, 338.2, 768.7, and 827.3 nm, and the hydrogen alpha Balmer series line at 656.3 nm. Line asymmetries are presented for the 328.0 nm Ag I line that is measured following generation of the plasma due to multiple photon absorption. This work explores electron density variations for different irradiance levels, and reports spectral line asymmetry of resonance lines for different laser fluence levels.

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of EdU⁺/αMHC-GFP⁺ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFP^high iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFP^low cells; however, S-phase synchronization didn’t enhance the polycistronic-MGT reprogramming, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

For esophageal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), restaging using F-18-fluorodeoxyglucose (18F-FDG) positron emission tomography computed tomography (PET-CT) following nCRT can detect interval metastases, including liver metastases, in almost 10% of patients. However, in clinical practice, focal FDG liver uptake, unrelated to liver metastases, is observed after chemoradiotherapy. This radiation-induced liver injury (RILI) can potentially lead to overstaging. Liver radiation damage is also a concern during distal esophageal cancer radiotherapy due to proximity to the left liver lobe, typically included in the radiation field. Post-CRT, if FDG activity appears in the left or caudate liver lobes, thorough investigation is needed to confirm or rule out distant metastases. The increased FDG uptake in liver lobes post-CRT often presents a diagnostic dilemma. Distinguishing between radiation-induced liver disease and metastasis is vital for appropriate patient management, necessitating a combination of imaging techniques and an understanding of the factors influencing radiation response. Diagnosis involves identifying new foci of hepatic FDG avidity on PET/CT scans. Geographic regions of hypoattenuation on CT and well-demarcated regions with specific enhancement patterns on contrast-enhanced CT scan and MRI are characteristic of radiation-induced liver disease (RILD). Lack of mass effect on all three modalities (CT, MRI, PET) indicates RILD. Resolution of abnormalities on subsequent examinations also helps in diagnosing RILD. Moreover, it can also help to rule out occult metastases, thereby excluding those patients from further surgery who will not benefit from esophagectomy with curative intent.

The efficacy of an intranasal (IN) bovine respiratory syncytial virus (BRSV) administered in the face of passive immunity was assessed. Pooled colostrum was administered by intubation to fifty (50) beef-dairy crossbred calves the day they were born. The calves were transported to a research facility and were blocked by age and sex and randomly assigned into two groups, a sham-vaccinated intranasally with a placebo (sterile water) or vaccinated with a tri-valent modified live viral (MLV) vaccine. The calves were 92 days old when vaccinated (day 0). The calves were challenged by aerosolized BRSV on day 80 and day 81 as a respiratory challenge. The study was terminated on day 88. Lung lesion scores (LLS) were significantly lower for calves vaccinated with tri-valent MLV vaccine than those for calves that were sham-vaccinated. Serum neutralization (SN) antibody against BRSV in calves vaccinated with the tri-valent MLV vaccine demonstrated an anamnestic response on day 88. After challenge, the calves sham-vaccinated with the placebo lost weight while those vaccinated with the tri-valent MLV vaccine gained weight. In this study colostrum-derived antibodies did not interfere with the immune response or protection provided by one dose of the tri-valent MLV vaccine.

The World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic in 2020, following which a global genetic vaccination program has been rapidly implemented as a fundamental solution. However, it has been reported worldwide that the modified mRNAs encoding spike proteins and lipid nanoparticles, which are used as drug delivery systems, not only cause thrombosis and cardiovascular disorders post vaccination, but might also cause diverse diseases involving all organs and systems, including the nervous system. Furthermore, the toxicity and pathogenicity of spike proteins may necessitate defining these proteins as nonbiological infective material. Based on these reports and the abundant evidence that has come to light in the past few years, this paper aims to draw the attention of medical professionals to the various risks associated with transfusion using blood products derived from long COVID patients or from genetic vaccine recipients, and to make proposals regarding specific inspection items, testing methods, regulations, etc. This paper provides insights to address the post-vaccination syndrome and its consequences following such genetic vaccination programs.

Introduction: Variants of COVID-19 are responsible for 700 million infections and 7 million deaths worldwide. Vaccinations have high efficiency in preventing infection and secondary benefits of reducing COVID-19 hospital admissions, attenuating disease severity and duration of illness. Conflicting reports were published regarding COVID-19 among PLWH. Objective: The aim of this study was to evaluate COVID-19 morbidity, hospitalization and the magnitude of immunological response to sequential BNT 162b2 mRNA vaccines in PLWH regarding demographic and clinical factors. Results: Our retrospective study included 784 PLWH who had at least one anti- SARS-CoV-2 antibody test between March 2021 and October 2021. Half of our patients (392) had CD4 cells count above 500 cells/µl, 40.2% (315) had 200<CD4<500 cells/µL and only 9.8% (77) had CD4 <200 cells/µL at their last laboratory workup. The mean age was 50.2±12.2 years. About 90% of our patients were given at least two doses of the BNT 1626b2 Pfizer vaccines, about 60% received three doses of the vaccine. About a quarter of our patients (27.3%) had COVID-19 infection. Only 6 patients required hospital admission. All six patients recovered from COVID-19 infection. Titers of COVID-19 antibodies were lower for patients with CD4 cells count of less than 200 cells/ µL in the first, second and third serological tests with statistical significance. In a multinomial logistic regression the influence of other factors such as age, sex, previous COVID-19 infection on first COVID-19 antibodies titers was not significant. Conclusions: PLWH are responsive to COVID-19 vaccines. As was expected, patients with higher CD4 cells count have higher titers of COVID-19 antibodies and less severe illness. Age, sex and previous COVID-19 infection did not significantly affect antibodies titers according to our study. Larger prospective studies with control groups are needed to further characterize immunologic response to COVID-19 vaccination among PLWH.

Background: Human papillomavirus (HPV) poses a significant health burden, yet the vaccine which successfully prevents HPV and its associated cancers remains underutilized. Nurses play a crucial role in patient education and advocacy for HPV vaccination. This study explores how knowledge, along with cultural, religious, and social beliefs, shapes the attitudes of Israeli nurses and nursing students toward the HPV vaccine and their advocacy efforts. Methods: A cross-sectional study was conducted from August 2023 to January 2024 using an anonymous online questionnaire distributed via Facebook groups targeting Israeli nurses and nursing students. The questionnaire assessed demographic data, HPV-related knowledge, and attitudes toward HPV vaccination. Results: The study included 458 participants (229 nurses and 229 nursing students). Significant knowledge gaps were found, with 52% of participants incorrectly believing that the vaccine can cure existing infections and 47% mistakenly believing that it is administered in a single dose. Logistic regression revealed that nurses working in community settings were more likely to have positive attitudes toward HPV vaccination (OR=2.98, 95% CI: 1.84–4.85). Higher levels of HPV-related knowledge (OR=3.35, 95% CI: 2.10–5.35) and secular or traditional religious affiliations (OR=2.45, 95% CI: 1.52–3.97) were strongly associated with positive attitudes toward and advocacy for the vaccine. Conclusions: Targeted educational programs addressing knowledge gaps, especially those tailored to Israel's cultural and religious diversity, are crucial for empowering nurses and nursing students as advocates for HPV vaccination. Enhancing their understanding of HPV can increase vaccine uptake, reduce the incidence of HPV-related diseases, and strengthen public health initiatives in Israel.

The effect of initial immunosuppressive therapy on the kinetics of the SARS-CoV-2 vaccine-induced humoral response is unknown. Here, we compared the kinetics of SARS-CoV-2 vaccine-induced humoral response in chronic kidney disease patients undergoing kidney transplantation (KTRs) and compared to patients remaining on dialysis during the Omicron circulation. This prospective, non-randomized, real-world study included 113 KTRs and 108 patients on dialysis. Those with previous COVID-19 or negative IgG at screening were excluded. Blood samples were collected to assess SARS-CoV-2 IgG titers and neutralizing antibodies at months (M) 1, 3, 6, and 12. Seroreversion occurred in 1 KTR and in 3 patients on dialysis. KTRs had lower IgG titers over time (M1: 10,809.3±12,621.7 vs. 15,267.8±16,096.2 IU/mL; M3: 12,215.5±12,885.8 vs. 15,016.2±15,346.1 IU/mL; M6: 12,540.4±13,010.7 vs. 18,503.5±14,581.0 IU/mL; p=0.005), but Neutralizing antibodies were similar (M1: 94.0 vs. 90.3%; M3: 92.9 vs. 90.5%; M6: 99.0 vs. 95.5%; M12: 98.9 vs. 97.5%; p=0.812). During follow-up, KTRs received more vaccine (141 vs. 73; p<0,001) and had more COVID-19 (32.7% vs. 14.8%; p=0.002). Compared to patients on dialysis, KTRs had lower SARS-CoV-2 IgG titers and similar rates of seroreversion and neutralizing antibodies over time. Although KTRs received more boosters, they had a higher incidence of COVID-19.

The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has exposed the vulnerabilities and unpreparedness of the global healthcare system in dealing with emerging zoonoses. In the past two decades, coronaviruses (CoV) have been responsible for three major viral outbreaks, and the likelihood of future outbreaks caused by these viruses is high and nearly inevitable. Therefore, effective prophylactic universal vaccines targeting multiple circulating and emerging coronavirus strains are warranted. This study utilized an immunoinformatic approach to identify evolutionarily conserved CD4+ (HTL) and CD8+ (CTL) T cells, and B-cell epitopes in the coronaviral spike (S) glycoprotein. A total of 132 epitopes were identified, with the majority of them found conserved in the bat CoV, pangolins CoV, endemic coronaviruses, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV). Their peptide sequences were then aligned and assembled to identify the overlapping regions. Eventually, two major peptide assemblies were derived based on their promising immune-stimulating properties. In this light, they can serve as lead candidates for universal coronavirus vaccine development, particularly in the search for pan-coronavirus multi-epitope universal vaccines that can confer protection against current and novel coronaviruses.

The vaccines have to undergo independent testing at National Control laboratory (NCL) for various quality control tests to ensure safety, purity, and potency before market authorization and surveillance testing. In this study, five different inactivated cell culture rabies vaccine preparations (Aluminum adjuvanted and non-adjuvanted) marketed in India were evaluated using compendial safety test of mouse inoculation test (MIT) for residual live virus. Investigations were done to see the interference of aluminum adjuvant in rabies vaccine preparation to ensure safety as per the in-vivo compendial test for virus inactivation. After intracerebral injections, mice received the aluminum phosphate adjuvanted inactivated rabies vaccine (ARV) had neurological complications that resulted in their deaths between days 4 and 10. Further investigations were carried out to find out the root cause for mice death including fluorescent antibody test (FAT), rabies virus amplification test. Additionally, alamar blue based cell cytoxicity assay was carried out using BHK-21 cells to estimate the cell toxicity of aluminum phosphate adjuvanted inactivated rabies vaccine. The present study highlighted the challenges in ensuring the safety of adjuvated inactivated rabies vaccine at level of NCL. Further, study demonstrated the toxicity of aluminum under both in vitro and in vivo settings, sparking controversy regarding the safety of aluminum adjuvants in vaccines at the suggested compendial limit of 1.25 mg/single human dosage.

One of the main objectives of developing new anti-cancer vaccine strategies is to effectively induce CD8+ T cell-mediated anti-tumor immunity. Live recombinant vectors, notably Listeria mono-cytogenes, have been shown to elicit a robust in vivo CD8+ T cell response in preclinical settings. Significantly, it has been demonstrated that Listeria induces inflammatory/immunogenic cell death mechanisms such as pyroptosis and necroptosis in immune cells that favorably control immunological responses. Therefore, we postulated that the host's response to Listeria-based vec-tors and the subsequent induction of CD8+ T cell-mediated immunity would be compromised by the lack of regulatory or effector molecules involved in pyroptosis or necroptosis. To test our hy-pothesis, we used recombinant L. monocytogenes carrying the ovalbumin gene (LM.OVA) to vac-cinate wild-type (WT), caspase-1/11-/-, gsdmd-/-, ripk3-/-, and mlkl-/- C57Bl/6 mice. We performed an in vivo cytotoxicity assay to assess the efficacy of OVA-specific CD8+ T lymphocytes in eliminat-ing target cells in wild-type and genetically deficient backgrounds. Furthermore, we evaluated the specific anti-tumor immune response in mice inoculated with B16F0 and B16F0.OVA mela-noma cell lines. Our findings demonstrated that while caspase-1/11 and GSDMD deficiencies in-terfere with the rapid control LM.OVA infection, of the KO seems to contribute to the early acti-vation of OVA-specific CTL responses. In contrast, individual deficiency of each one of these pro-teins negatively impact the generation of long-lasting effector CD8+ T cells.

The control of classical swine fever (CSF) in endemic areas has been attempted with modified live vaccines. However, in some regions, the implementation of imperfect vaccination programs has led to a reduction in the genetic diversity of the circulating strains and a change in their virulence. Porvac® subunit vaccine has been shown to provide a rapid onset of protection against the “Margarita” strain. The aim of this study was to evaluate whether the immune response induced by Porvac® is also effective against autochthonous isolates of low, medium or high virulence. All pigs vaccinated with Porvac® were protected against the disease after the challenge. PR-11/10–3 isolate caused a very mild disease in controls, whilst Holguin_2009 isolate produced mild to moderate signs of CSF and one of the pigs died. Finally, controls inoculated with PR-2016 isolate developed moderate to severe signs of CSF and two of them died. Viral replication was detected in controls, but not in pigs immunized with Porvac®. Finally, anti-Erns antibodies were induced in five out of six control pigs but in any of the vaccinated pigs. These results support the use of Porvac® for the control and elimination of CSF in Cuba and other endemic regions.

Purpose: Post-pandemic management of COVID-19 infections and any emergent outbreaks is as an endemic disease remains a public health concern. Vaccine hesitancy may continue to hamper efforts to respond any new disease outbreaks and future epidemics. This qualitative study aimed to explore factors influencing covid-19 vaccine acceptance and hesitancy in Kenya too gain deeper insights on this issue. Methods: The study was implemented in Western Kenya using key informant interviews. Fourteen (14) key informants were purposively selected for the study. All interviews were transcribed and analyzed using thematic analysis. Interpretation of findings was done within the framework of the Health Belief Model. Key findings: Knowledge was a critical factor in combatting misinformation and fostering vaccine acceptance among participants in this study. Misinformation included rumors that the vaccine lowers immunity and was intended for population control. Cues to action included influence from political and opinion leaders and observing the loss of life among unvaccinated individuals. Perceived barriers to vaccine uptake included fear of vaccine safety, side effects, long waiting times at that time of our study, fear of contracting the COVID-19 at vaccination sites, family/spousal influence on vaccine uptake and fear of the unknown with the vaccine. Conclusion: Findings from this study provides insight into areas for targeted strategies for managing Covid-19 vaccinations and future pandemics. Within the framework of the Health Belief Model, this study identified salient barriers and facilitators of COVID-19 vaccine hesitancy that may be helpful to inform future pandemic response.

The emergence of the H3N2 influenza virus in 1968 marked a significant event as it crossed the species barrier. Since then, ongoing mutational dynamics have led to the formation of antigenic clusters, prompting the World Health Organization to advocate for regular updates to H3N2 vaccines. Research in the Western Pacific region underscores the necessity for heightened awareness and effective control strategies. Stemming from avian influenza A, the 1968 H3N2 influenza pandemic resulted in the deaths of one million people globally, with its seasonal variants primarily affecting older individuals and causing severe illness due to antigenic drift. To address the challenge of vaccine efficacy against H3N2 mutations, researchers are exploring innovative strategies such as precise antigenic material administration, controlled release patterns, understanding immune system mechanisms, and glycan engineering. This review comprehensively examines various aspects of the Influenza A (H3N2) virus, encompassing its virological characteristics, evolutionary trends, global epidemiology, vaccination strategies, antiviral interventions, and emerging diagnostic approaches. It underscores the impact of antigenic variation on vaccine design and effectiveness, seasonal outbreak patterns, pandemic potential, and the interplay between viral factors and host immune responses. Moreover, the review evaluates antiviral therapies and the issue of drug resistance, emphasising the necessity for multidisciplinary approaches involving researchers, healthcare professionals, and policymakers to comprehend H3N2 and enhance public health interventions.

Gardasil 4, a human papilloma virus vaccine, has been shown to protect against various cancers, including cervical cancer. Common side effects include injection site pain, fever, headaches, and muscle aches. In some individuals, the severe side effect of postural orthostatic tachycardia syndrome (POTS) has been reported. POTS is characterized by the abnormal response of lightheadedness, blurry vision, and dizziness while transitioning to an upright posture. POTS predominately affects women, with more than eighty-five (85) percent of POTS patients being female. POTS on average, takes five years and eleven months to receive the diagnosis. Additionally, ​A strong association between POTS and Ehlers Danlos Syndrome Type III (EDS) exists. Eighty (80) percent of patients with EDS have POTS. This severe side effect dictates that providers need to be aware of this strong association of HPV vaccinations and POTS. ​In this report we will present a case of a young women with a past medical history significant for EDS type III who was diagnosed with POTS after receiving Gardasil 4 vaccination. This case demonstrates the need for physicians to be aware of the association of POTS with EDS type III and HPV vaccination. Physician awareness of the associations, signs and symptoms of POTS and earlier testing at the first presentation of signs and symptoms will limit the negative impact on patient’s quality of life.

Stallion mules have been used as working equids in several countries. Aggressiveness, under the influence of testosterone, resulted in the necessity for surgical castration before work training. The gonadotropin-releasing hormone (GnRH) vaccine may be an alternative method for immunocastration in mules. The objectives were to evaluate the effect of GnRH vaccine on anti-GnRH antibody production, serum testosterone level, clinical adverse effects, and behavior toward human manipulation. Twenty-five mules were separated into 3 groups: Control-intact, Control-castrated, and Treatment. Treatment was further divided into subgroups according to condition (intact or unilateral cryptorchid) and age. Treatment received 195 µg GnRH vaccine intramuscularly at week 0, 4, and 8. Anti-GnRH antibody increased at week 6 and 10, then gradually decreased to baseline at week 22. Treatment-intact-young had the highest anti-GnRH antibody, resulting in lower serum testosterone levels during week 2-6 and 12-16 compared to Control-intact. Subcutaneous edema adjacent to the injection site was detected only in Treatment-intact after booster vaccination. During week 6-22, the behavioral scores of Treatment significantly changed toward at ease with human contact compared to a score before vaccination. In conclusion, mules responded to GnRH vaccine, which could temporarily suppress testosterone for up to 16 weeks.

COVID-19 vaccine hesitancy and its enablers would shape community uptake of non-covid vaccines such as oral cholera vaccine (OCV) in the post-COVID-19 era. This study assessed the impact of COVID-19 vaccine hesitancy and its drivers on OCV hesitancy in a cholera endemic region of the Democratic Republic of Congo. We conducted a community-based survey in Bukavu. The survey included characteristics, intention to take OCV and COVID-19, reasons for COVID-19 hesitancy, and thinking and feeling about COVID-19 vaccines. Poisson regression analyses were performed. Of the 1708 respondents, 84.66% and 77.57% were hesitant to OCV alone and to both OCV and COVID-19, respectively. Hesitancy to COVID-19 vaccines rose OCV hesitancy by 12% (crude Prevalence Ratio, [cPR]=1.12, 95%CI[1.03-1.21]). Independent predictors of OCV hesitancy were living in semi-urban area (adjusted Prevalence Ratio [aPR]=1.10, 95%CI[1.03-1.12]), religious refusal of vaccines (aPR=1.06, 95%CI[1.02-1.12]), concerns about vaccine safety (aPR=1.05, 95%CI[1.01-1.11]) and adverse effects (aPR=1.06, 95%CI[1.01-1.12]), as well as poor knowledge (aPR=1.07, 95%CI[1.01-1.14]). Conversely, the belief about COVID-19 vaccine effectiveness reduced OCV hesitancy (aPR=0.76, 95%CI[0.62-0.93]). COVID-19 vaccine hesitancy and its drivers exhibiting a significant domino effect on OCV uptake. Addressing vaccine hesitancy through community-based health literacy interventions would likely improve the introduction of novel non-COVID-19 vaccines in post-COVID-19 era.

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individual’s resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled, re-vaccinated with two doses of Shanchol™ regardless of previous vaccination and followed-up for 90 days. Bloods collected at baseline before re-vaccination, at day 14 prior to second dosing and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60 and 90 across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

Coronavirus disease 2019 (COVID-19), the global pandemic caused by severe acute respiratory syndrome 2 virus (SARS-CoV-2) infection, has caused millions of infections and fatalities worldwide. Extensive SARS-CoV-2 research has been conducted to develop therapeutic drugs and prophylactic vaccines, and even though some drugs have been approved to treat SARS-CoV-2 infection, treatment efficacy remains limited. Therefore, preventive vaccination has been implemented on a global scale and represents the primary approach to combat the COVID-19 pandemic. Approved vaccines vary in composition, although vaccine design has been based on either the key viral structural (spike) protein or viral components carrying this protein. Therefore, mutations of the virus, particularly mutations in the S protein, severely compromise effectiveness of current vaccines and the ability to control COVID-19 infection. This review begins by describing the SARS-CoV-2 viral composition, mechanism of infection, role of angiotensin-converting enzyme 2, host defense responses against infection and the most common vaccine designs. Next, this review summarizes the common mutations of SARS-CoV-2 and how these mutations change viral properties, confer immune escape and influence vaccine efficacy. Finally, this review discusses global strategies that have been employed to mitigate the decreases in vaccine efficacy encountered against new variants.

The human immunodeficiency virus (HIV) continues to pose a significant global health challenge, with millions of people affected and new cases emerging each year. While various treatment and prevention methods exist, including antiretroviral therapy and non-vaccine approaches, developing an effective vaccine remains the most crucial and cost-effective solution to combat the HIV epidemic. Despite significant advancements in HIV research, the HIV vaccine field has faced numerous challenges, and only one clinical trial has demonstrated a modest level of efficacy. This review delves into the history of HIV vaccines and the current efforts in HIV prevention, emphasizing pre-clinical vaccine development using the non-human primate model (NHP) of HIV infection. NHP models offer valuable insights into potential preventive strategies for combating HIV, and they play a vital role in informing and guiding the development of novel vaccine candidates before they can proceed to human clinical trials.

The introduction of three single nucleotide mutations into the genome of the virulent RVFV ZH548 strain allows the rescue of a fully attenuated virus in mice (ZH548-rA2). These mutations are located in the viral genes encoding the RdRp and the non-structural protein NSs. This paper shows the results obtained after subcutaneous inoculation of ZH548-rA2 in adult sheep and subsequent challenge with the parental virus (ZH548-rC1). Inoculation with ZH548-rA2 virus caused no detectable clinical or pathological effect in sheep, whereas inoculation of the parental rC1 virus caused lesions compatible with viral infection characterized by the presence of scattered hepatic necrosis. Viral infection was confirmed by immunohistochemistry, with hepatocytes within the necrotic foci appearing as the main cells immunolabelled against viral antigen. Furthermore, inoculation of sheep with rA2 virus prevented the liver damage expected after rC1 virus inoculation, suggesting a protective efficacy in sheep which correlated with the induction of both humoral and cell mediated immune responses.

Despite recent public health and hygiene advancements, enteric fever, commonly referred to as typhoid fever, remains a common disease in developing nations. The common mode of infection is contaminated water or food. Additionally, person-to-person transmission through poor hygiene and sewage contamination of water supplies has been blamed for most outbreaks. The exact burden of typhoid has yet to be discovered because of the lack of surveillance systems in many developing nations. This makes it difficult to estimate the number of cases. Recent studies have shown that the actual number of cases of typhoid has been estimated to be around 21.6 million annually. The mortality studies suggest that the incidence of typhoid is highest in children under five years old. Typhoid fever and paratyphoid fever have been demonstrated to be life-threatening illnesses. Salmonella serotype Typhi (S. Typhi) is the causative organism of typhoid fever whereas Salmonella serotype Paratyphi is the causative organism for paratyphoid fever. The S. Typhi bacterium is known to be resistant to various drugs. There is a dire need to develop new drugs to treat and overcome the current drug-resistant S. Typhi. The identification of new targets marks the beginning of the process of developing new anti-S. Typhi drugs. The S. Typhic genome sequencing and recent cutting-edge molecular biology tools have led to the discovery of numerous new inhibitors and targets. The goal of this review is to identify the most critical targets in the S. Typhi that are targeted by drugs. It also highlights the various promising vaccines on the market or are still in preclinical studies. A detailed understanding of the targets could help researchers develop safer and more efficient antibacterial agents against S. Typhi.Additionally, the advancement of molecular techniques and the knowledge of the Salmonella pathogenesis pathways have opened better avenues to develop effective antibiotics and vaccines against this pathogen. This review also sought to identify and summarize critical structures of this pathogen that play significant roles in the maturation, development, and pathogenesis of S. Typhi. The endpoint of this work is to provide valuable information on potential therapeutic targets of S. Typhi for drug and vaccine developers.

To investigate the early immune responses and explore the optimal vaccination periods, Nile tilapia at 1, 7, 14, 21, 28, 35, and 42 days after yolk sac collapse (DAYC), were immersed in formalin-killed Streptococcus agalactiae vaccine (FKV-SA). The results found that specific IgM by ELISA in 21 DAYC (0.108 g) was first detected at 336 h after vaccination (hav), whereas 28-42 DAYC (0.330 - 0.580 g), could be initially detected at 24 hav. qRT-PCR analysis of the TCRβ, CD4, MHCIIα, IgHM, IgHT, and IgHD genes at 21- 42 DAYC immunized with FKV-SA immersion route for 24, 168 and 336 hav, revealed that most immune-related genes were significantly higher in the vaccinated larvae in all DAYCs than the control larvae (P &lt; 0.05) after 336 hav. Immunohistochemistry demonstrated the stronger signals of IgM in the gills, head kidney, and intestine tissues at 21, 28, and 35 DAYC were observed in all vaccinated larvae compared with the control. Interestingly, at all DAYCs, FKV-SA larvae exhibited significantly higher survival rates and an increased relative percent survival (RPS) than the control after challenge with viable S. agalactiae, particularly in larval fish that were immunized with FKV-SA for 168 and 336 hav (P &lt; 0.05).

In mammals, the role of interleukin-18 (IL-18) in the immune response is to drive inflammatory and, normally therefore, anti-viral responses. IL-18 also shows promise as a vaccine adjuvant in mammals. Chicken IL-18 (chIL-18) has been cloned. The aim of this study was to investigate the potential of chIL-18 to act as a vaccine adjuvant in the context of a live recombinant Fowlpox virus vaccine (fpIBD1) against Infectious bursal disease virus (IBDV). fpIBD1 protects against mortality, but not against damage to the bursa of Fabricius caused by IBDV infection. The Fowlpox virus genome itself contains several candidate immunomodulatory genes, including potential IL-18 binding proteins (IL-18bp). We have knocked out (Δ) the potential IL-18bp genes in fpIBD1 and inserted (::) the cDNA encoding chIL-18 into fpIBD1 in the non-essential ORF030, generating five new viral constructs –fpIBD1::chIL-18, fpIBD1ΔORF073, fpIBD1ΔORF073::chIL-18, fpIBD1ΔORF214 and fpIBD1ΔORF214::chIL-18. The subsequent protection from challenge with virulent IBDV, as measured by viral load and bursal damage, given by these altered fpIBD1 strains, was compared to that given by the original fpIBD1. The results show that chIL-18 can act as a vaccine adjuvant, giving complete protection against challenge, with no detectable virus or damage in the bursa of Fabricius.

Despite numerous studies on cancer treatment, cancer remains a challenging disease to cure, even after decades of research. In recent years, cancer vaccine has emerged as a promising approach for cancer treatment, offering few unexpected side effects compared to existing therapies. How-ever, cancer vaccine faces obstacles to commercialization due to its low efficacy. Particularly, the Toll-like receptor (TLR) adjuvant system, specifically the TLR 7/8 agonist, has shown potential for activating Th1 immunity, which stimulates both innate and adaptive immune responses through T cells. In this study, we developed ProLNG-S, a cholesterol-conjugated form of resiquimod (R848), to enhance immune efficacy by stimulating the immune system and reducing toxicity. ProLNG-S was formulated as ProLNG-001, a positively charged liposome, and co-administered with oval-bumin (OVA) protein in the B16-OVA model. ProLNG-001 effectively targeted secondary lym-phoid organs, resulting in a robust systemic anti-tumor immune response and tumor-specific T cell activation. Consequently, ProLNG-001 demonstrated potential for preventing tumor progression and improving survival compared to AS01 by enhancing anti-tumor immunity.

The development of efficient mucosal vaccines is strongly dependent on the use of appropriate vectors. Various biological systems or synthetic nanoparticles have been proposed to display and deliver antigens to mucosal surfaces. The Bacillus spore, a metabolically quiescent and extremely resistant cell, has also been proposed as a mucosal vaccine delivery system and shown able to conjugate the advantages of live and synthetic systems. Several antigens have been displayed on the spore by either recombinant or non-recombinant approaches, and antigen-specific immune responses have been observed in animals immunized by the oral or nasal route. Here we review the use of the bacterial spore as a mucosal vaccine vehicle focusing on the advantages and drawbacks of using the spore and of the recombinant vs. non-recombinant approach to display antigens on the spore surface. An overview of the immune responses induced by antigen-displaying spores so far tested in animals is presented and discussed.

How to optimally allocate COVID-19 vaccines and scarce public goods is a crucial and sensitive question to scholars, policy-makers, and practitioners. The ethical dimensions and principles of vaccine allocation between groups are widely agreed upon, whereas the ethical dimensions and principles of vaccine distribution between countries at the peak of the COVID-19 pandemic are highly controversial. This article aims to investigate how vaccines were globally allocated across countries and propose an optimal allocation mechanism for vaccines and scarce public goods. The results show that, to a certain extent, the global allocation of COVID-19 vaccines was fair and effective. Countries with more cases and deaths obtained more vaccines and vaccinations. Wealthier countries might receive more vaccinations but also suffer more severe consequences of COVID-19. Though COVAX could miss its initial vaccine delivery targets, the facility should be considered successful in its core goals and plays a critical role in controlling the pandemic. The study proposes a fair and effective mechanism of vaccine allocation that combines the roles of markets and interventions of international organizations and national governments with three degrees: emergency, priority, and market.

There is a lack of information on vaccination for pregnant women in the Brazilian literature. Our aim was to evaluate the data on vaccines recorded on the pregnancy card and knowledge about the importance of vaccination for women admitted for labor in a reference public tertiary maternity unit in Presidente Prudente, São Paulo, Brazil. Vaccine data as prescribed by the National Immunization Program of Brazil (NIP) in prenatal cards for patients in labor from the 45 municipalities of the western region of São Paulo state were obtained. A questionnaire relating to knowledge about the types and importance of vaccination in pregnancy was applied. All vaccines indicated by the NIP were registered in only 12.0% of the prenatal cards, and 33.0% of cards registered any vaccines. In this group, 16.6% were aged between 14 and 21 years, and tetanus and COVID-19 were the most prevalent vaccines that they had heard of during prenatal care. Data on vaccines was poorly recorded in the cards, suggesting a lack of attention and unpreparedness of professionals working in primary care. Our study has countrywide and global relevance, and may be applied mainly in Latin American countries facing similar difficulties and limitations with low rates of vaccination during pregnancy.

Abstract Background COVID-19 vaccination program among Adults in India is one of the highly successful vaccination drives globally. Indian children aged 15–18 years old became eligible for COVID-19 vaccination on 3rd January, 2022 followed by 12-14 years old children on 16th March, 2022. As parents are primary decision-makers for their children, we aimed to assess parents' perceptions and intentions regarding COVID-19 vaccination for children in India. Aim To assess parental perceptions and intention to get COVID-19 vaccination for their children (aged<18 years), Materials and Methods A cross-sectional anonymous web-based survey was designed. Healthcare workers of a tertiary care institute in Eastern U.P. having any children aged <18 years were the study population. They were recruited through snowball sampling and were sent the study questionnaire in Google form through email and WhatsApp. Cross-tabulation was performed by parents' intention to vaccinate their children against COVID-19 virus with socio-demographic characteristics and their risk perception toward COVID-19, trust in the healthcare system, and their history of vaccine hesitancy behavior routine childhood immunization. Bi-variate analysis was performed to find out the predictors of child vaccination intention among the parents. Results A total of 388 healthcare workers parents (HCWPs) having A child < 18 years of age completed the survey. Mean age of the parents were 40.28 ±11.34 years with majority(97.0%) completing recommended 2 doses of COVIID-19 vaccine. Around 91% of the parents agreed that COVID-19 vaccines are important for child’s health whereas about 89% agreed to the statement that COVID-19 vaccines are effective. A total 356 (91.7%) participants were willing to vaccinate their child against COVID-19, 91.3% of them liked to do so as soon as possible. The factors significantly associated with the stated likelihood of child vaccination among the participants were younger age, female gender, urban residence, absence of any chronic illness, lower monthly income, history of COVID-19 in child and the child/children completed with routine childhood vaccines. Parental concerns mainly centered around vaccine need, safety and side effects. Conclusion The healthcare worker parents(HCWPs) have good knowledge and positive attitude towards COVID-19 vaccination for children. Around 92% of them were willing to vaccinate their children with COVID vaccine currently, which implies very low vaccine hesitancy among the HCWPs . Further longitudinal studies are required to be conducted to assess the trend of parental acceptance of COVID vaccine.

The emergence of drug-resistant parasitic nematodes of both humans and livestock calls for development of alternative and cost-effective control strategies. For the economically important ruminant strongylid Haemonchus contortus, Barbervax® remains the only registered vaccine available. Here we compared the microbiome, genome-wide diversity and transcriptome of H. contortus adult male populations that survived vaccination with an experimental vaccine after inoculation in sheep. Our genome-wide SNP analysis revealed 16 putative candidate vaccine evasion genes. However, we did not identify any evidence for changes in microbial community profiling based of 16S rRNA gene sequencing results of vaccine surviving parasite populations. A total of 58 genes were identified as significantly differentially expressed with six being long non-coding (lnc) RNAs and no putative candidate SNP associated genes. The genes highly upregulated in surviving parasites from vaccinated animals were associated with GO terms belonging to predominantly molecular function and a few biological processes that may have facilitated evasion or potentially lessened the effect of the vaccine. These included five targets: astacin (ASTL), carbonate dehydratase (CA2), phospholipase A2 (PLA2), glutamine synthetase (GLUL) and fatty acid-binding protein (FABP3). We searched all five DEG targets against the proteomes of selected Nematoda (Clades III, V, IV, C, I) and Platyhelminthes (Clades Monogenea, Trematoda, Cestoda, Rhabditophora) to determine homologs within the H. contortus NZ_HCO_NP v1.0 genome and identified single-copy orthologous groups (OGs) in selected proteomes. All but one (FABP3) demonstrated high levels of duplication and wide-spread occurrence in closely related Caenorhabditis elegans and Pristionchus pacificus, with complete absence of all five gene targets among other Clade III (Toxocara canis) and V (Ascaris suum, Ascaris lumbricoides and Parascaris univalens) nematodes, further supporting their vital biological functions in nematodes. Phylogenetic analyses inferred the presence of only ASTL and CA2 in almost all Nematoda, platyhelminthes and metazoans examined, with loss of GLULs observed among all outgroup vertebrate species and the presence of FABP3 in only three other species (Schmidtea mediterranea, Fasciola gigantica and F. hepatica). Our tertiary structure predictions and modelling analyses were used to perform in silico searches of all published and commercially available inhibitor molecules or substrate analogues with potential broad-spectrum efficacy against nematodes of human and veterinary importance.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused more than 600 million cases and over 6 million deaths worldwide. Vaccination has been the main strategy used to contain the spread of the virus, and to avoid hospitalizations and deaths. Currently, there are two mRNA-based and one adenovirus vectored vaccines approved and available for use in the U.S. population. The versatility, low cost and rapid-to-manufacture attributes of DNA vaccines are important advantages over other platforms. However, DNA vaccination must meet higher efficiency levels for use in humans. Importantly, in vivo DNA delivery combined with electroporation (EP) has been successfully used in the veterinary field. Here we evaluated the safety, immunogenicity and protective efficacy of a novel linear SARS-CoV-2 DNA vaccine candidate for delivered by intramuscular injection followed by electroporation (Vet-ePorator™) in ferrets. The results demonstrated that the linear SARS-CoV-2 DNA vaccine candidate did not cause unexpected side effects, and was able to elicit neutralizing antibodies and T cell responses using a low dose of the linear DNA construct in prime-boost regimen, and significantly reduced shedding of infectious SARS-CoV-2 through oral and nasal secretions in a ferret model.

Healthcare workers (HCWs) are regarded as role models regarding health-related issues including vaccination. Therefore, it is essential to identify the predictors for COVID-19 vaccine acceptance among them. A cross-sectional study to assess the risk perception, attitudes and knowledge of HCWs toward COVID-19 vaccination was carried out. A total of 710 responses were received between September 2021 to March 2022, from HCWs in the Northern, Western and Eastern regions of Nigeria. Cross tabulations were performed to determine statistical relations between sociodemographic variables, knowledge, attitudes and risk perceptions concerning COVID-19 vaccine acceptance. Multinomial Logistic Regression analysis was performed to determine the predictive variables for COVID-19 vaccine acceptance. Statistical analyses were performed and P-values less than 0.05 were considered statistically significant at a CI of 95%. Results showed that 59.3% of the participants were amenable to COVID-19 vaccines. Multinomial regression analysis identified 14 variables at α <0.05 as predictors for vaccine acceptance. Male HCWs were 2.8 times more likely to accept the vaccine than their female counterparts. HCWs that were knowledgeable of the different kinds of vaccines, willing to recommend the vaccines to their patients, believe that the timing of COVID-19 vaccination was appropriate and had recent vaccination history within three years were 1.6, 24.9, 4.4 and 3.1 times more likely to take COVID-19 vaccine than those not sure. The study found a relatively high trust (51.3%) in the Nigerian Center for Disease Control (NCDC) for information regarding COVID-19 vaccines. Therefore, the NDCD should disseminate more robust insights regarding the safety profiles of various COVID-19 vaccines.

Vaccination is the most promising approach for ending or containing the SARS-CoV2 pandemic. However, serious post-COVID vaccine reactions including immunocytopenia (ITP) syndrome has been increasingly reported. Several factors cause increased risks including multiple doses, age-dependent heterogeneity in immune-responses, platelet cross-reactions with microbial components, and Long-COVID syndrome. Thus, in the absence of a widely available specific therapeutics, vigilance is important while more studies are imperative. Using a structured questionnaire sent to different regions in Saudi Arabia, we conducted a comprehensive investigation on the frequency, rates, disease patterns, and patient demographics of post-COVID-19 side effects on febrile patients after three major vaccines. Results indicated the majority administered Pfizer BioNtech vaccine (81%, n=809); followed by AstraZeneca (16%, n=155); and Moderna (3%, n=34). In overall 998 participants, 74% (n=737) had no serious symptoms; however, 26.2% (n=261) revealed typical syndrome. In a focused group of 722, shortness of breath (20%), bruises or bleeding (18%), inattention (18%), GIT symptoms (17.6%), skin irritation (8.6%), and anosmia and ageusia (8%) were the most prominent. The onset time was mostly in 1-3 days in 49% (n=128), followed by 4-7 days in 21.8% (n=57), 8-14 days in 16.5% (n=43), and more than a month in 12.6% (n=33). The onsets occurred mostly after the first, second, or both doses 9%, 10%, and 7%, respectively. The frequency of symptoms was significantly higher among after Moderna ® vaccine (P-value = 0.00006) and it was significantly lower in participants who received Pfizer (P-value 0.00231). We did not find significant difference in symptoms related to differences in regions. Similarly, the region, age, gender, education, and nationality had no influence in the dose and onset timings. The findings of this study have significant clinical implications in disease management strategies, preventive measures, and vaccine development. Future vertical studies would reveal more insights into the mechanisms of post-COVID vaccine syndrome.

Marburg virus disease (MVD) is a hemorrhagic fever and cause death up to 88% of people and is the same as Ebola virus, It is transmitted through skin contact or mucous membrane in the eyes, nose or mouth with blood or body fluids like urine, saliva sweat, feces and by object contaminated with body fluids. Despite these facts, yet there is no approved vaccine have been developed for the eradication of Marburg virus infections. Therefore, this study described a multi epitope-based peptide vaccine against Marburg virus viral protein 35, using several immunoinformatics tools combined with molecular docking studies. Utilizing Vaxijen 2.0 server, the V35 protein revealed to be antigenic with a score of 0.4316. Prediction of the T-cell and B-cell epitopes was then conducted. RTFDAFLGV epitope was found to be the most promising one with binding affinity to the highest numbers of MHC I alleles, a positive score in the Class I immunogenicity study and non-allergen. These results were further confirmed by the good interaction of RTFDAFLGV to the groove of HLA-A*02:01 with binding energy of -8.1 kcal/mole. Finally, the vaccine was cloned in silico to ensure its validity and efficiency of expression. To ensure its safety and immunogenic profile, in-vitro and in-vivo bioassays are recommended to confirm these findings.

Although vaccinating the world is adopted by the WHO to limit COVID-19 transmission, people’s worries about vaccines may suppress their desire for vaccination despite vaccine availability. This study aimed to evaluate the levels of stress and anxiety among 250 Jordanians who received their first vaccine dose at a local community health center. The respondents completed the stress and anxiety subscales of the Depression Anxiety and Stress scale 21 (DASS-21) pre- and post-vaccination. The respondents expressed more moderate-severe levels of stress pre than post vaccination (20.8% and 13.2%, respectively). Meanwhile, 37.2% and 45.2% of the respondents expressed moderate-severe anxiety pre and post vaccination, respectively. Wilcoxon signed-rank test revealed that the drop in the level of stress from pre (median (IQR) = 5 (1-8)) to post vaccination (median (IQR) = 3 (1-7)) was statistically significant (z = -3.81, p = 0.001, r = 0.17) while the increase in anxiety was not. Anxiety median significantly dropped among individuals experiencing mild to severe anxiety pre vaccination. Similarly, stress and anxiety significantly increased among individuals expressing normal anxiety pre vaccination (z = -3.57 and -8.24, p values = 0.001, r = 0.16 and 0.37, respectively). Age positively correlated with post vaccination anxiety among respondents with mild pre vaccination anxiety, and it negatively correlated with pre vaccination level of stress in the normal anxiety group. Gender, marital status, respondents’ level of education, and history of COVID-19 infection had no significant correlation with anxiety or stress at either point of measurement. Overcoming their hesitancy to receive COVID-19 vaccine, individuals with normal levels of anxiety experienced a rise in their distress symptoms following immunization. On the contrary, vaccination seemed to desensitize anxious individuals. Policymakers need to formulate a population-specific plan to increase vaccine preparedness and promote psychological well-being over all during the pandemic.

Background: Relatively little is known and inconclusive about social inequality in human papillomavirus (HPV) vaccination among teenagers in the United States. This study aims to investigate whether there is a social disparity in HPV vaccination among teenagers and if so, whether it can differ by the source of teen vaccination information (parental reports and provider records). 
Methods: We used the data from the 2019 National Immunization Survey-Teen (NIS-Teen; 42,668 teenagers, aged 13-17) including parental reported vaccination status. Among them, 18,877 teenagers had adequate provider reported vaccination records. Two socioeconomic status (SES) measures were used: mother’s education and annual family income. Multivariate logistic analyses were conducted. 
Results: False negatives of parental reports against provider records were more than two times higher (p < 0.001) in low SES teens than in high SES teens. In both SES measures, the proportion of HPV unvaccinated teenagers were lowest in the highest SES level in analyses with parental reports. However, it was the opposite in analyses with provider records. Interestingly, regardless of vaccination information source, the HPV unvaccinated rate was highest in the middle SES teens (>12 years, non-college graduates; and above poverty level, but not > $75K). 
Conclusion: A significant social inequality in HPV vaccination among teenagers exists in the United States. The pattern of social inequality in HPV vaccination can be distorted when only parent reported vaccination information is used.

Aleutian mink disease virus (AMDV) is known to cause the most significant disease in the mink industry. It is globally widespread and manifested as a deadly plasmacytosis and hyperglobulinemia. So far, measures to control viral spread have been limited to manual serological testing for AMDV-positive mink. Further, due to the persistent nature of this virus, attempts to eradicate Aleutian disease (AD) have largely failed. Therefore, effective strategies to control viral spread are of crucial importance for wildlife protection. One potentially key tool in the fight against this disease is by immunization of mink against AMDV. Throughout many years, several researchers have tried to develop AMDV vaccines and demonstrated varying degrees of protection in mink by those vaccines. Despite these attempts, there are currently no vaccines available against AMDV, allowing the continuation of the spread of Aleutian disease. Herein, we summarize previous AMDV immunization attempts in mink as well as other preventative measures with the purpose to shed light on future studies designing such a potentially crucial preventative tool against Aleutian disease.

Tilapia lake virus (TiLV) is the main tilapia-infecting virus worldwide, causing serious economic losses. However, there is no vaccine for this viral disease. Here, TiLV ORF10 (TiLV-ORF10) encoding a protein with abundant epitopes was constructed into the eukaryotic expression vector pcDNA3.1, and used to evaluate the immune protective effects in Nile tilapia (Oreochromis niloticus). RT-PCR and western blot analyses confirmed vaccine plasmid expression in tilapia muscle tissues. Moreover, the transcription levels of immunoglobulin M, toll-like receptor 2, myeloid differentiation factor 88, interleukin 8, tumor necrosis factor alpha, gamma-IFN, and nuclear factor κB immune-related genes were statistically significantly upregulated in the spleen, liver, and kidney of vaccinated tilapias (P < 0.05). TiLV challenge experiments showed that relative percent survival (RPS) was significantly enhanced in fish by this DNA vaccine. Moreover, RPS was enhanced further when using a higher amount of the DNA vaccine (85.72% RPS at a DNA dose of 45 μg pcDNA3.1–ORF10). Vaccination with pcDNA3.1–ORF10 significantly reduced virus replication, as evidenced by the low amount of virus in the spleen, liver, and kidney of vaccinated tilapias after TiLV challenge. Thus, pcDNA3.1–ORF10 could induce protective immunity in tilapia and may be a potential vaccine candidate for controlling diseases caused by TiLV.

This review critically assesses the body of research about Measles-Mumps-and-Rubella (MMR) vaccine attitudes and uptake in the United Kingdom (UK) over the past 10 years. We searched PubMed and Scopus, with terms aimed at capturing relevant literature on attitudes, uptake, decision-making, and beliefs about the MMR vaccine. Two researchers screened for abstract eligibility and after de-duplication 934 studies were selected. After screening, 40 references were included for full-text review and thematic synthesis by three researchers. We were interested in the methodologies employed, and grouped findings by whether studies concerned: (1) Uptake and Demographics; (2) Beliefs and Attitudes; (3) Healthcare Worker Focus; (4) Experimental and Psychometric Intervention; (5) Mixed Methods. We identified group and individual level determinants for attitudes, operating directly and indirectly, that influence vaccine uptake. We found that access issues, often ignored within the public “anti-vax” debate, remain highly pertinent. Finally, a consistent theme was the effect of misinformation and lack of knowledge or trust in healthcare, often stemming from the Wakefield controversy. Future COVID-19 immunisation campaigns for children should consider both access and attitudinal aspects of vaccination, and incorporate a range of methodologies to assess progress, taking into account socio-economic variables and the needs of disadvantaged groups.

Immune complexes (ICs) made of antibody-bound antigens exhibit immunomodulatory activities exploitable in a vaccination strategy to optimize vaccine efficacy. The modulatory effects of ICs are typically attributed to the Fc fragments of the antibody components, which engage Fc receptors, complement and complement receptors on various immune cells. These Fc-mediated functions facilitate the critical interplay between innate and adaptive immune systems to impact the quality and quantity of the elicited adaptive responses. In addition to the Fc contribution, the Fab fragment also plays an immunoregulation role. The antigen-binding domains of the Fab fragment can bind their specific epitopes at high affinity to sterically occlude these antigenic sites from recognition by other antibodies. Moreover, the Fab-mediated binding have been demonstrated to induce allosteric alterations at nearby or distant antigenic sites. In this review article, we survey published studies to illuminate how the immunomodulatory functions of ICs have been investigated or utilized in a vaccination strategy to fight against an array of infectious pathogens, culminating with IC vaccine designs aimed at preventing HIV-1 infection. In particular, we highlight IC vaccine candidates that exploit Fab-mediated steric and allosteric effects to direct antibody responses away or toward the V1V2 domain, the V3 loop, and other antigenic sites on the HIV-1 envelope gp120 glycoprotein. Like other HIV-1 vaccine approaches, the path for IC-based vaccines to reach the clinic faces major hurdles yet to be overcome; however, investigations into this vaccine strategy have provided insights into the multifaceted activities of antibodies beyond their conventional roles in the host defense against HIV-1 and other microbial pathogens.

In the present day and age, cancer is still a life-limiting factor whose one of the therapeutic strategies is immunotherapy with vaccines. This research aims to prepare and characterize nanoliposomal vaccine formulation attached to HER2/neu-derived peptide (AE36) with or without CpG-ODN, and to evaluate its immunological responses to the therapy using BALB/c mice with HER2 overexpressing breast cancer. Methods: AE36 was conjugated to the liposomes containing DOTAP, DOPE and Cholesterol. Such formulations are able to produce CD8+ and CD4+ responses and induce synthesis of cytokines detectable via Enzyme-linked immunosorbent assay kits, cytotoxicity testing and intracellular cytokine staining combined with flow cytometry. Therapeutic and prophylactic effectiveness were evaluated through the formulation in samples. The highest effectiveness was found in DDC-peptide + CpG-ODN in both prophylactic and therapeutic studies, which decreased the size of tumors significantly and increased time of survival. These nanoliposomes linked to AE36 could be regarded as an appropriate candidate for the treatment and also for prophylaxis of HER2+ breast cancer; however further studies are needed.

We reviewed the association between seasonal influenza vaccination and the risk of SARS-CoV-2 infection or complicated illness or poor outcome (e.g. severe disease, need for hospitalization or ventilatory support, or death) among COVID-19 patients. None of the studies that were reviewed (n=12) found a significant increase in the risk of infection or in the illness severity or lethality, while some reported significantly inverse associations. Our findings support measures aimed at raising influenza vaccination coverage in the coming months.

As the number of infections and deaths caused by the recent COVID-19 pandemic is increasing dramatically day-by-day, scientists are rushing towards developing possible counter-measures to fight the deadly virus, SARS-CoV-2. Although many efforts have already been put forward for designing and developing potential vaccines, however, most of them are proved to possess negative consequences. Therefore, in this study, the methods of immunoinformatics were exploited to design novel epitope-based subunit vaccine against the SARS-CoV-2, targeting four essential proteins of the virus i.e., spike glycoprotein, nucleocapsid phosphoprotein, membrane glycoprotein, and envelope protein. The highly antigenic, non-allergenic, non-toxic, non-human homolog and 100% conserved (across other isolates from different regions of the world) epitopes were used for constructing the vaccine. In total, fourteen CTL epitopes and eighteen HTL epitopes were used to construct the vaccine. Thereafter, several in silico validations i.e., the molecular docking, molecular dynamics simulation (including the RMSF and RMSD studies), and immune simulation studies were also performed which predicted that the designed vaccine should be quite safe, effective, and stable within the biological environment. Finally, in silico cloning and codon adaptation studies were also conducted to design an effective mass production strategy of the vaccine. However, more in vivo and in vitro studies are required on the predicted vaccine to finally validate its safety and efficacy.

SARS-CoV-2 has been the talk of the town ever since the beginning of 2020. The pandemic has brought the complete world on a halt. Every country is trying all possible steps to combat the disease ranging from shutting the complete economy of the country to repurposing of drugs and vaccine development. The rapid data analysis and widespread tools, software and databases have made bioinformatics capable of giving new insights to the researchers to deal with the current scenario more efficiently. Vaccinomics, the new emerging field of bioinformatics uses concepts of immunogenetics and immunogenomics with in silico tools to give promising results for wet lab experiments. This approach is highly validated for the designing and development of potent vaccines. The present in-silico study was attempted to identify peptide fragments from spike surface glycoprotein that can be efficiently used for the designing and development of epitope-based vaccine designing approach. Both B-cell and T-cell epitopes are predicted using integrated computational tools. VaxiJen server was used for prediction of protective antigenicity of the protein. NetCTL was studied for analyzing most potent T cell epitopes and its subsequent MHC-I interaction through tools provided by IEDB. 3D structure prediction of peptides and MHC-I alleles (HLA-C*03:03) was further done to carry out docking studies using AutoDock4.0. Various tools from IEDB were used to predict B-cell epitopes on the basis of different essential parameters like surface accessibility, beta turns and many more. Based on results interpretation, the peptide sequence from 1138-1145 amino acid and sequence WTAGAAAYY and YDPLQPEL were obtained as a potential B-cell epitope and T-cell epitope respectively. This in-silico study will help us to identify novel epitope-based peptide vaccine target in spike protein of SARS-CoV-2. Further, in-vitro and in-vivo study needed to validate the findings.

Currently, with a large number of fatality rates, coronavirus disease-2019 (COVID-19) has emerged as a potential threat to human health worldwide. It has been well-known that severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is responsible for COVID-19 and World Health Organization (WHO) proclaimed the contagious disease as a global pandemic. Researchers from different parts of the world amalgamate together inquest of remedies for this deadly virus. Recently, it has been demonstrated that the spike glycoprotein (SGP) of SARS-CoV-2 is the mediator behind the entrance into the host cells. Our group has comprehensibly analyzed the SGP of SARS-CoV-2 through multiple sequence analysis along with the phylogenetic analysis. Further, this research work predicted the most immunogenic epitopes for both B-cell and T-cell. Notably, we focused mainly on major histocompatibility complex (MHC) class I potential peptides and predicted two epitopes; WTAGAAAYY and GAAAYYVGY, that bind with the MHC class I alleles which are further validated by molecular docking analysis. Furthermore, this study also proposed that the selected epitopes were shown availability in a greater range of the population. Hence, our study comes up with a strong base for the implementation of designing novel vaccine candidates against SARS-CoV-2, however adequate laboratory works will need to be conducted for the appropriate application.

Purpose: This review features a generalized overview of dengue outbreaks, dengue pathogenesis, symptoms, immune response, diagnosis methods and preventive measures which facilitates the better understanding of the global expansion and concerns relating to the disease. Recent Findings: A recent study showed that natural killer cells of the infected person become activated soon after the infection which may help in treatment and vaccine development. A research team has also produced synthetically engineered mosquitoes that can prevent the transmission and dissemination of the dengue virus by the activation of an antibody. Furthermore, a mutation in the protein envelope of the dengue virus leads to variation in shapes, developing resistance towards the vaccine. Summary: The increasing number of reported cases indicated the worldwide distribution of the mosquito vectors, which was further facilitated by the growth in the shipping and commerce industries. The immune system, through activation of the innate and adaptive immune responses, facilitates the recruitment of an array of leukocytes which help neutralize the virus. However, the 4 different viral serotypes increases the risk of a life-threatening secondary infection due to the varying serotypes. Apart from the laboratory standard PRNT method, several other dengue detection methods such as ELISA, RT-LAMP and several optical, microfluidic and electrochemical methods have been developed. Since Dengvaxia® (CYD-TDV) has its own set of drawbacks and limitations, several companies have been investing for the production of more potential vaccines that are currently in trial.

DNA vaccines are stable, safe, cost effective to produce and relatively quick and easy to manufacture. However, to date DNA vaccines have shown relatively poor immunogenicity in humans despite promising preclinical results. Consequently, a number of different approaches have been investigated to improve the immunogenicity of DNA vaccines. These include the use of improved delivery methods, adjuvants, stronger promoters and enhancer elements to increase antigen expression, and codon optimization of the gene of interest. This review describes the creation and use of a DNA vaccine vector containing a porcine circovirus (PCV-1) enhancer element that significantly increases recombinant antigen expression and immunogenicity and allows for dose sparing. A 172bp region containing the PCV-1 capsid protein promoter (Pcap) and a smaller element (PC; 70 bp) within this were found to be equally effective. DNA vaccines containing the Pcap region expressing various HIV-1 antigens were found to be highly immunogenic in mice, rabbits and macaques, at 4 to 10-fold lower doses than normally used and to be highly effective in heterologous prime-boost regimens. By lowering the amount of DNA used for immunization, safety concerns over injecting large amounts of DNA into humans can be overcome.

Meningitis is a severe disease associated with death in children under five with highest rates of infections under age of one. Vaccines for Neisseria meningitides and Haemophilus influenza are used to prevent the main causative agents of meningitis. Administration of H. influenzae type b (Hib) vaccine is recommended at 2, 4 and 6 months with a booster dose at 18 months. N. meningitidis has two commercially available vaccines, the pure polysaccharide is recommended at 24 months meanwhile the protein-conjugated vaccines at 12 months. We sought in this study to examine if coadministering the vaccines for the two main meningitis causing bacteria might be synergistic as a preliminary step towards the possibility of shuffling immunization schedule. So, we coadministered Hib vaccine with commercially available vaccines either quadrate (ACWY) polysaccharide meningococcal (Men) or conjugated meningococcal (Nim) vaccines in Balb/C mice (n = 6/group) and compared to each vaccine administered separately and controls. Thirty-five days post immunization, we measured specific antibodies titers. Hib vaccine increased Men antibody titers significantly for serotypes Y and W. When Hib vaccine was coadministrated with Nim, antibody titer for Y, W and A significantly increased. For serotype C, there was no significant difference in antibody titers among immunized groups. As for effect of meningococcal vaccines on Hib, Men significantly increased Hib antibody titers while Nim had no effect. Collectively, our data suggested that coadministration of Hib and Men or Nim vaccines was safe and had synergistic effect on immune responses elicited to both vaccines. Further studies are needed before immunization schedule modifications. Such immunization schedule recommendation should provide better protection against this life-threatening disease in young children.

Abstract: Thermostability of vaccines, particularly enveloped viral vectored vaccines, remains a challenge for their delivery wherever needed. Freeze-drying of viral vectored vaccines is a prom-ising approach but remains challenging due to the water removal process from the outer and in-ner parts of the virus. In the case of enveloped viruses, freeze-drying induces increased stresses on the envelope, which often leads to inactivation of the virus. In this study, we design a method to freeze-dry a recombinant Vesicular Stomatitis Virus (VSV) expressing the SARS-CoV-2 spike glycoprotein. Since the envelope of VSV is composed of 50% lipid and 50% protein, the formula-tion study focused on both the protein and lipid portions of the vector. Formulations were pre-pared primarily using sucrose, trehalose, and sorbitol as cryoprotectants; mannitol as a lyopro-tectant; and histidine as a buffer. Initially, the infectivity of rVSV-SARS-CoV-2 and cake stability were investigated at different final moisture contents. High recovery of the infectious viral titer ( 0.5 to 1 log loss) was found at 3-6% moisture content with no deterioration of the freeze-dried cakes. To further minimize infectious viral titer loss, the composition and concentration of the ex-cipients were studied. An increase from 5 to 10% of both cryoprotectants and lyoprotectant, to-gether with the addition of 0.5% gelatin, resulted in the improved recovery of infectious virus titer and stable cake formation. Moreover, the secondary drying temperature of the freeze-drying pro-cess showed a significant impact on the infectivity of rVSV-SARS-CoV-2. The infectivity of the vector declined drastically when the temperature was raised above 20°C. Throughout a long-term stability study, formulations containing 10% sugar (sucrose/trehalose), 10% mannitol, 0.5% gelatin, and 10 mM of histidine showed satisfactory stability for six months at 2-8°C. The development of this freeze-drying process and the optimized formulation minimizes the need for a costly cold chain distribution system.

Background: The aim of this study was to investigate the degree of penetration, permanence of occlusion and vascular changes induced by a newly modified mixture of n-butyl cyanoacrylate (Glubran 2®), ethanol, and Lipidol® (GEL) in endovascular treatment of experimental aneurysms induced in swine. Methods: Bilateral pouch aneurysms were created in the wall of the internal carotid artery in eighteen pigs. The sixteen aneurysms were treated with a new mixture of GEL with different component proportions. Angiograms were obtained at the time of treatment and at 1, 4, and 16 weeks after treatment. According to the scheduled experimental design, subjects were sacrificed at the time of treatment and 7, 30, and 90 days after embolization of experimentally induced aneurysms. The internal carotid artery and aneurysms were resected en bloc and fixed for histopathologic study. Results: All the experimentally induced aneurysms were completely occluded by the used mixture and remained occluded for the study period without recanalization. Histopathologic studies revealed the presence of an acute inflammatory reaction of aneurysm wall even after 7 days post embolization with focal angionecrosis, followed by a chronic inflammation which induced a thickening of the wall. Conclusions: The mixture succeeded to induce a complete occlusion which remained stable until 90 days post-embolization. After seven days from embolization, the mixture polymerization was associated with an acute inflammatory response followed by a connective tissue proliferation which induced a thickening of aneurysm walls.

Post-exercise recovery is fundamental to optimizing athletic performance, focusing on muscle repair, glycogen replenishment, rehydration, and reducing exercise-induced inflammation. This review examines the evolving landscape of recovery nutrition, highlighting the transition from conventional supplements—such as protein, carbohydrates, creatine, and branched-chain amino acids (BCAAs)—to functional foods rich in bioactive compounds. Emerging evidence supports the efficacy of functional foods like tart cherry juice, turmeric, and omega-3 fatty acids in mitigating oxidative stress and inflammation, thus accelerating recovery. Additionally, probiotics and prebiotic-rich foods are gaining recognition for enhancing gut health, promoting nutrient absorption, and strengthening immune function, which are crucial in recovery processes. The concept of personalized nutrition, guided by genetic and metabolic profiling, is explored as a promising approach to tailor recovery strategies to individual physiological needs. Continued research into the long-term effects of supplements, the role of functional foods, and nutrient interactions is essential for developing more comprehensive and individualized recovery protocols. Integrating functional foods with personalized nutrition offers a holistic strategy to enhance recovery, optimize performance, and promote long-term health in athletes.

There is increasing evidence that COVID-19 induces endothelial dysfunction that may precede thrombotic and cardiovascular complications. The aim of this study is to evaluate the endothelial function using peripheral arterial tonometry (EndoPAT). The primary endpoint is the hyperemic vascular response index (LnRHI) at two months post-discharge. Secondary endpoints include the LnRHI during hospitalization and at six months follow-up, the proportion of patients with endothelial dysfunction (LnRHI≤0.51), and the incidence of thrombotic events, cardiovascular complications, and mortality during the follow-up period. The study included 23 COVID-19 patients and 22 healthy matched controls. The patients exhibited a significant reduction in the LnRHI at two months post-discharge compared to the controls (median=0.55 [IQR: 0.49-0.68] vs median=0.70 [IQR: 0.62-0.83]; p=0.012). The difference in the LnRHI between patients and controls was evident from hospitalization and persisted at two and six months without significant temporal changes. The proportion of COVID-19 patients with endothelial dysfunction (LnRHI≤0.51) was 61% during hospitalization, and 55% at six months. There was no significant difference in thrombotic or cardiovascular events, nor in mortality. This study demonstrates that COVID-19 adversely affects endothelial function, as evidenced by a reduction in the hyperemic vascular response index, and the endothelial dysfunction may also persist.

Anaerobic digestion has the potential to convert organic waste materials into valuable energy. At the same time, using press water from biomass materials for energy generation, while taking advantage of the resulting cake for other purposes is an emerging approach. Therefore, this study aimed to investigate the residual potential expected from a typical biogas feedstock in the West African context after it has been mechanically separated into liquid and solid phases. Hence, in this study, the rumen contents of ruminants (cow, goat and sheep) and their proportionate ratios were obtained from an abattoir in Ghana. Resource characterisation of the waste samples were carried out in the Central laboratory of the HFR, Germany. Anaerobic batch tests for biogas (biomethane) yield determination were set-up using the Hohenheim Biogas Yield Test (HBT). Inoculum used was obtained from an inoculum production unit at the Hohenheim University biogas laboratory. The trial involved two different forms of the sample: mixture of rumen contents, press water, and inoculum, each in four (4) replicates. The trial was carried out at a mesophilic temperature of 37°C. Results obtained over a seventy (70) day period were transformed into biogas yields. Overall, the results show that the current contents are suitable for biogas generation as an option, as opposed to the current form of disposal at a refuse dump. However, using these mixtures in their original forms is more technically viable than using press water without further treatment.

This study provides a comprehensive analysis of the conformational dynamics of pseudo-endocannabinoid receptors (p-CBRs) CB₁ and CB₂ in response to ligand binding. The ligands studied include N-arachidonoyl dopamine (NADA), Cannabidiol (CBD), known agonists (FUB-MDMB and E3R), and inverse agonists (Taranabant and AM630). Using homology models based on crystal structures (PDB ID: 5U09 for CB₁ and 5ZTY for CB₂), molecular docking, and molecular dynamics (MD) simulations, the research validates the structural integrity and dynamic behaviours of these pseudo-receptors. Induced-fit docking revealed NADA as having the highest binding affinity for both receptors, with docking scores of −13.92 kcal/mol for CB₁ and −13.32 kcal/mol for CB₂, facilitated by key hydrogen bond interactions. MD simulations over 250 ns at ~298 K showed successful equilibration, indicating the most stable interaction for NADA, thereby further validating the models. CB₁ and CB₂ exhibited distinct conformational responses to ligands, with Cα RMSD and Cα RMSF analyses suggesting a more rigid binding pocket for CB₁ and a flexible binding pocket for CB₂. These findings highlight the significance of receptor behaviour and dynamics in the development of cannabinoid-based therapeutics, supporting the potential of CBD and NADA as modulators for CB₁ and CB₂, respectively.

Excessive oxidative stress and exercise-induced fatigue reduce physical performance and can lead to dysfunction in antioxidant systems within muscular and hepatic tissues. Integrating natural substances with exercise may mitigate fatigue via anti-oxidant effects. This study aims to compare and evaluate the effects of exercise and supplementation with Sundarbans honey vs energy drinks on the strength, anxiety physiological profiles, and hepatic antioxidant capacity in mice undergoing extraneous exercise and fatigue. Forty-eight four-week-old Swiss albino mice were randomly assigned to one of eight groups: (1) Control, (2) Speed™ (Sp), (3) Royal Tiger™ (RT), (4) Sundarbans Honey (SH), (5) Exercise (Ex), (6) Exercise + Sundarbans Honey (Ex+SH), (7) Exercise + Speed™ (Ex+Sp), and (8) Exercise + Royal Tiger™ (Ex+RT). Supplements were administered via oral gavage: Sp (2.5 ml/kg BW), RT (2.5 ml/kg BW), and SH (1 g/kg BW), four times a week for 60 days. Mice in the Ex, Ex+SH, Ex+Sp, and Ex+RT groups underwent daily swimming and running. The strength, fatigue, anxiety levels, lipid profiles, and antioxidant biomarkers were evaluated post-treatment. The SH, Ex, and Ex+SH groups exhibited significantly enhanced physical performance (p<0.05). Plasma lipid profiles, including LDL, triglycerides, total cholesterol, and fatigue-related biomarkers (ALP, AST, ALT, LDH, CK, LA, BUN, and glucose) were markedly increased in the Sp and RT groups but decreased in the SH, Ex, and Ex+SH groups compared to control (p<0.05). Exercise-induced fatigue elevated the Nrf2/HO-1 antioxidant defense system in liver tissue. IL-6 levels were reduced in the SH, Ex, and Ex+SH groups (p<0.05). These findings indicate that regular exercise combined with SH supplementation increases strength and improves lipid profiles, reducing exercise-induced oxidative stress and fatigue via modulation of the Nrf2/HO-1 pathway in liver tissue. These results highlight SH supplementation’s potential as a complementary strategy to enhance exercise outcomes and mitigate exercise-induced stress.

Thermally-induced moisture flow in unsaturated soils is a complex coupled thermal-hydro process involving moisture flow both in vapor and liquid phases. Thermally-induced moisture flow in unsaturated sands is usually less pronounced than fine soils due to their low field capacity. It is affected by many factors, including soil density, particle size, moisture content, and gravity-induced flow. Besides, soil moisture sensors need to be highly accurate and calibrated for temperature effects in order to monitor the thermally induced moisture flow accurately. A silty sand with 35% non-plastic fines was selected to study the coupled thermo-hydro processes in a closed heat cell. The heat cell consists of two temperature-controlled heat exchanger plates at the top and bottom, heat flux sensors, moisture sensors, thermocouples, and heat conductivity sensors. The soil was prepared at various initial moisture content and tested under a constant 1-D temperature gradient. The soil moisture sensors were first calibrated in the test soil at room temperature and then at elevated temperatures. The soil moisture redistribution, temperature and thermal conductivity profiles were determined. The critical moisture content, corresponding to maximum moisture movement, was also determined. The results offer new insights into coupled moisture-heat flow in unsaturated sands.

Exercise-induced muscle injury is one of the most common types of sports injuries. Skeletal muscle troponin I (skTnI) serves as an ideal biomarker in assessing such injuries, facilitating timely detection and evaluation. In this study, we develop a fluorescent sandwich lateral flow immunoassay (LFIA) combined with a desktop analyzer for rapid detection of skTnI. Through optimizing the reaction system, the assay achieves a satisfying detection performance, reaching a limit of detection (LOD) of 0.5 ng/mL with a turnaround time of 15 minutes. The proposed de-tection platform offers portability, ease of use, and high sensitivity, which facilitates the moni-toring of exercise-induced muscle injuries at the point of care. This feature is particularly advan-tageous for end-users, enabling timely detection of sports-related injuries and ultimately en-hancing prognosis and sports life.

The Qiushuwan Cu-Mo deposit, located in the East Qinling molybdenum belt, which is a major mining site recognized for its enormous reserves of medium-sized molybdenum. In order to enhance our comprehension and ascertain supplementary mineral resources, it is critical to conduct an in-depth investigation of both the deep and peripheral regions. The primary goal of this study is to investigate the Qiushuwan Copper Molybdenum Mine, which is located in Zhenping County, Henan Province. The spread spectrum-induced polarization (SSIP) method is utilized as a means of conducting mining exploratory analysis. Significant findings have been obtained through the collection of SSIP data, geological analysis, and electrical parameter study of rock and ore samples along profile-80. By conducting a meticulous examination of the SSIP data at suitable frequencies, two prominent conductive ore bodies, specifically C2 and C4, have been successfully discovered. C2 exhibits a correlation with granite porphyry and molybdenum veins, while C4 is linked to a skarn deposit that contains a concentration of copper ore. The spatial differences in conductivity within the research area have been precisely characterized using resistivity models obtained from the SSIP data. The precision and dependability of our conclusions have been confirmed through the integration of borehole data and the matching of geological sections with inversion models. The recovered core samples show a diverse range of minerals, containing both valuable ores and minerals that have undergone alteration. Pyrite constantly appears with molybdenite in the majority of samples. The aforementioned results provide a strong foundation for future exploration initiatives and sustainable resource exploitation, enabling informed decision-making in the effective use and administration of natural resources. This study adds to the existing body of knowledge on the Qiushuwan Cu-Mo deposit and improves exploration methods in the region by utilizing the SSIP approach. The findings are a useful asset for geologists, mining experts, and stakeholders, offering essential knowledge for future exploration and sustainable utilization of resources.

Successful geophysical exploration works in Gucheng-Yaxi area located in Gaochun District, Jiangsu province, China, have been limited partly due to complex geological condition of the area and high artificial noise in data acquired using electrical and electromagnetic methods. In this work, we deployed the new anti-interference spread spectrum induced polarization method (SSIP) and audio magnetotellurics (AMT) method to detect a copper-polymetallic deposit in the area. Two-dimensional (2D) inversion results at Gucheng-Yaxi Area revealed a high chargeability anomalous zone on SSIP profile that coincided with a zone of moderate resistivity located between two resistor bodies on AMT profile. A follow up 1200 meters drill hole was established at this high chargeability-moderate resistivity zone which encountered polymetallic (copper, lead, zinc, gold and silver) mineralization at the depth ≥ 400 m. Drill hole data analysis showed that mineralization occurs interspaced in marble rock mass at varies depth. Furthermore, several low resistivity-weak chargeability sections were revealed and inferred attributed to Cretaceous sediments and faults. These faults are thought to have played critical role in the polymetallic mineralization genesis. In summary, this work demonstrated the successful of application of SSIP and AMT at detecting a metallic deposit in an area with high artificial noise. Hence the geophysical prospection potential of Gucheng-Yaxi area is great.

Earthquake-triggered landslides are one of the most significant hazards worldwide. These landslides, involving small or large volumes, can develop in debris flow or avalanche with high mobility and long-runout distance. The motion processes of this kind of landslide also quite complicated. This study reproduced the motion processes of two landslides using the LS-RAPID program. The Aso Bridge landslide occurred on April 16, 2016, with rapid and long-runout distance characteristics. The Kataragai landslide occurred on April 9, 2018, travelling with flow-like behavior. Through field investigations and laboratory experiments, features and mechanical parameters of these two landslides were obtained. In the LS-RAPID program, the pre-failure models and motion processes of these two landslides were established and reproduced. Results indicated that sliding speed and travelling morphology at different intervals were considered as two indicators to describe their motion process. However, while sliding speed of these two landslides have significant differences with sliding speeds of actual landslides, the final morphologies after failure were consistent with those observed in the field investigation.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene located on chromosome 16 (16p13.3) and coding pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of pathological processes leading to autoinflammation observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool for studying the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs of an Armenian patient with FMF having M694V, p.(Met694Val) (c.2080A&gt;G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. In addition, we found that the morphology of patient macrophages derived from iPSCs with MEFV mutation was significantly different from that of differentiated from iPSCs of a healthy donor carrying wild-type MEFV gene.

The exceptional performance of graphene has driven the advancement of its preparation technique and application. Laser-induced graphene (LIG), as a novel graphene preparation technique, has been applied in various fields. Graphene periodic structures created by LIG technique exhibit superhydrophobic characteristics and can be used for deicing and anti-icing applications, which are significantly influenced by the laser parameters. The laser surface treatment process was simulated by a finite element software analysis (COMSOL Multiphysics) to optimize the scanning parameter range, and the linear array surface structure were subsequently fabricated by the LIG technique. The generation of graphene was confirmed by Raman spectroscopy, and energy-dispersive X-ray spectroscopy. The periodic linear array structure were observed by Scanning electron microscopy (SEM) and confocal laser imaging (CLSM). In addition, CLSM testings, contact angle measurements, and delayed icing experiments were systematically performed to investigate the effect of scanning speed on surface hydrophobicity. The results show that the high quality and uniform graphene can be achieved using the laser scanning speed of 125 mm/s. The periodic linear array structures can obviously increase the contact angle and suppress delayed icing. Furthermore, these structures have the enhanced ability of the electric heating deicing, which can reach 100°C and 240°C within 15 s and within 60 s under the DC voltage power supply ranging from 3 to 7 V, respectively. These results indicate that the LIG technique can be developed to provide an efficient, economical, and convenient approach for preparing graphene and the hydrophobic surface array structure based on LIG has considerable potential for deicing and anti-icing applications.

The availability of multi-rotor UAVs with lifting capacities of several kilograms, allows for a new paradigm in atmospheric measurement techniques, i.e. the integration of research-grade sonic anemometers for airborne turbulence measurements. With their ability to hover and move very slowly, this approach yields an unrevealed flexibility compared to mast-based sonic anemometers, for a wide range of boundary layer investigations that require an accurate characterization of the turbulent flow. For an optimized sensor placement, potential disturbances by the propeller-induced flow (PIF), as well as the potential impact of the sensor weight and angular momentum on the flight performance in the case of a boom-mounted sensor, have to be considered.

Plant cells are omnipotent and breeding of new varieties can be achieved by protoplast fusion. Such fusions can be achieved by treatment with poly(ethylene glycol) or by applying an electric field. Microfluidic devices allow for controlled conditions and targeted manipulation of small batches of cells down to single cell analysis. To provide controlled conditions for protoplast fusions and achieve high reproducibility, we developed and characterized a microfluidic device to reliably trap few of Arabidopsis thaliana protoplasts and induced a cell fusion by controlled addition of poly(ethylene glycol) (PEG, with a molecular weight of 6000). Experiments were conducted to determine the survival rate of isolated protoplasts in our microfluidic system. Afterwards, PEG induced fusion was studied. Our results indicate that the following fusion parameters had significant impact on the fusion efficiency and duration: PEG concentration, osmolarity of solution, and flow velocity. PEG concentration below 10% led to only partial fusion. Osmolarity of the PEG fusion solution was found to strongly impact the fusion process; complete fusion of two source cells sufficiently took part in slightly hyper osmotic solutions, whereas iso-osmotic solutions led to only partial fusion at 20% PEG concentration. We observed accelerated fusion for higher fluid velocities. Up to this study, it was common sense that fusion is one directional, i.e. once two cells were fused into one cell they stay fused. Here, we present for the first time reversible fusion of protoplasts. Our microfluidic device paves the way to a deeper understanding on the kinetics and processes of cell fusion.

RNA, as an important substance for regulating biological growth and development, has significant implications for visualization research. However, many spontaneously fluorescent substances in plants greatly interfere with the effectiveness of plant bioimaging. Aggregetion- induced emission luminogens (AIEgens), due to their luminescent properties, tunable molecular size, high fluorescence intensity, good photostability, and low cell toxicity, have been widely applied in the animal and medical fields. We have found that AIEgens have great potential as RNA fluorescent probes for efficient imaging in plants. In this review, we first introduce several common RNA labeling forms and point out their pros and cons. We briefly describe the development of AIEgens and the AIE mechanism, and then present various practical applications of AIEgens, including detailed examples of their use as biological markers. To further promote the application of AIE in the field of RNA, we suggest the use of AIEgens to modify target RNA via techniques such as click chemistry or CRISPR/Cas, to achieve RNA visualization in plants. highly possible to modify target RNA with AIEgens in vivo for RNA visualization.

Laser-induced periodic surface structures (LIPSS) have gained significant attention due to their ability to modify the surface morphology of materials at the micro-nanoscale and show great promise for surface functionalization application. In this study, we specifically investigate the formation of LIPSS in silicon substrates and explore their impact on Surface-Enhanced Raman Spectroscopy (SERS) applications. This study reveals a stepwise progression of LIPSS formation in silicon, involving three distinct stages of LIPSS: 1) integrated Low-Spatial-Frequency LIPSS (LSFL) and High-Spatial-Frequency LIPSS (HSFL), 2) principally LSFL and 3) LSFL at the edge of the irradiated spot, elucidating the complex interplay between laser fluence, pulse number, and resulting surface morphology. Furthermore, from an application standpoint, these high-quality multi-scale periodic patterns lead to the next step of texturing the entire silicon surface with homogeneous LIPSS for SERS application. The potential of LIPSS-fabricated silicon substrates for enhancing SERS performance is investigated using thiophenol as a test molecule. The results indicate that the Au-coated combination of LSFL and HSFL substrate showcased the highest enhancement factor (EF) of 1.38 × 10^6. This pronounced enhancement is attributed to the synergistic effects of Localized Surface Plasmon Resonance (LSPR) and Surface Plasmon Polaritons (SPPs), intricately linked to HSFL and LSFL characteristics. These findings contribute to understanding LIPSS formation in silicon and their applications in surface functionalization and SERS, paving the way for sensing platforms.

The theory of electron spin has been proposed for a century, but the study of quantum effects in biological molecules is still in its infancy. Chirality-induced spin selectivity (CISS) is a very modern theory that can explain many biochemical phenomena. In this paper, we propose a new theoretical model based on CISS theory and quantum chemistry theory, which can well explain the theoretical explanation of the chiral selectivity of chiral proteins. Moreover, this theory can predict the spin state of corresponding chiral molecules. Taking L-DOPA and AADC enzyme as examples, this theoretical model solves the theoretical explanation of AADC enzyme's chiral catalysis selectivity problem and successfully predicts the spin state of L-DOPA and D-DOPA's valence electrons.